General ideas about the structure of various muscles
Many cells have a limited ability to convert chemical energy into mechanical force and movement, but only in muscle fibers has this process taken center stage. The main function of these specialized cells is to generate force and movement, which the body uses to regulate the internal environment and move in the external space.
Based on the structure, contractile properties and regulatory mechanisms, three types of muscle tissue are distinguished:
1) skeletal muscles;
2) smooth muscles;
3) cardiac muscle (myocardium).
Skeletal muscles, as their name implies, are usually attached to the bones of the skeleton; thanks to the contractions of these muscles, the position of the skeleton in space is maintained and its movements occur. Contractions occur under the influence of impulses from nerve cells and are usually arbitrary.
Figure 4-1A shows skeletal muscle fibers (top panel), cardiac muscle cell (middle panel), and smooth muscle cell (bottom panel). The skeletal muscle cell is called muscle fibre. During embryonic development, each muscle fiber is formed by the fusion of many undifferentiated mononuclear cells. (myoblasts) into one cylindrical multinucleated cell. Differentiation skeletal muscle completed around the time of birth. In the period from infancy to adulthood, the sizes of differentiated muscle fibers continue to increase, but new fibers are not formed from myoblasts. In an adult, the diameter of muscle fibers reaches 10-100 microns, the length is up to 20 cm.
If skeletal muscle fibers are damaged in the postnatal period, they cannot be replaced by division of the remaining fibers, but new fibers are formed from undifferentiated cells, the so-called satellite cells, located next to muscle fibers and undergoing differentiation similar to embryonic myoblasts. The possibilities for the formation of new fibers in the skeletal muscle are significant, however, after severe damage, it is not completely restored. Important role in compensation
lost muscle tissue plays an increase in intact muscle fibers.
In the figure fig. 4-1 A, D also shows the heart muscle (myocardium), which ensures the work of the heart.
Layers smooth muscles are located in the walls of hollow internal organs and tubular formations: stomach, intestines, bladder, uterus, blood vessels, bronchi. As a result of contractions of smooth muscles, the contents of hollow organs are pushed through, the flow of fluid in the vessels and ducts is regulated by changing their diameter. Small bundles of smooth muscle cells are also found in the skin around the hair follicles and in the iris. Smooth muscle contractions are controlled by the autonomic nervous system, hormones, autocrine/paracrine factors, other local chemical signals. Some smooth muscles contract spontaneously even in the absence of signals. Unlike skeletal muscle, smooth muscle is not voluntary.
Despite the significant differences between these three types of muscles, they have a similar mechanism for generating force. Skeletal muscles will be considered first, then smooth muscles. The cardiac muscle is characterized by a combination of a number of properties of the first two types of muscles.
The most remarkable characteristic of skeletal and also cardiac muscle fibers when studied with a light microscope is the alternation of light and dark stripes transverse to the long axis of the fiber. Due to this feature, both types of muscles are classified as striated muscles (Fig. 4-1A, upper and middle panels). This pattern is absent in smooth muscle (Fig. 4-1A, lower panel).
IN skeletal muscle thick and thin filaments form a periodic pattern along each myofibril. The regularly repeating element of this pattern is known as sarcomere(from the Greek sarco - muscle, mere - small) (enlarged fragment in Fig. 4-1 B). Each sarcomere includes triad:
1) the cistern of the sarcoplasmic reticulum;
2) transverse tubule;
3) another cistern of the sarcoplasmic reticulum (Fig. 4-1 B).
Figure 4-1B shows the structure of smooth muscle, which is different from skeletal muscle.
Combined Figure 4-1D shows a synchronous recording of action potentials, as well as a mechanogram of the skeletal muscle and the heart muscle.
Rice. 4-1. Organization of fibers and filaments in skeletal and smooth muscle
Muscle types
There are three types of muscles: skeletal, smooth and myocardial. Skeletal muscles are attached to bones for support and movement. Smooth muscles surround the hollow and tubular organs. The heart muscle (myocardium) provides the work of the heart.
Skeletal muscles
1. Skeletal muscles consist of cylindrical muscle fibers (cells); each end of the muscle is connected by tendons to the bones.
2. Skeletal muscle fibers are characterized by a periodic alternation of light and dark bands, reflecting the spatial organization of thick and thin filaments in myofibrils.
3. Thin filaments containing actin are attached at both edges of the sarcomere to the Z-bands; the free ends of thin filaments partially overlap with myosin-containing thick filaments in the A-band of the central part of the sarcomere.
4. During active shortening of the skeletal muscle fiber, thin filaments are pulled towards the center of the sarcomere as a result of movements of myosin cross-bridges that bind to actin:
The two globular heads of each cross bridge contain an actin-binding site, as well as an ATP-cleaving enzyme;
Each work cycle of the cross bridge consists of four stages. During contraction, the cross-bridges make repeated cycles, each of which provides a very small advance of thin filaments;
ATP performs three functions during muscle contraction.
5. In a resting muscle, the attachment of transverse bridges to actin is blocked by tropomyosin molecules in contact with thin filament actin subunits.
6. Reduction is initiated as a result of an increase in the cytoplasmic concentration of Ca 2+ . When Ca 2+ ions bind to troponin, its conformation changes, due to which tropomyosin is displaced, opening access to binding sites on actin molecules; cross bridges are associated with thin filaments:
An increase in the cytoplasmic concentration of Ca 2+ is triggered by an action potential
plasma membrane. The action potential extends deep into the fiber along the transverse tubules to the sarcoplasmic reticulum and causes the release of Ca 2+ from the reticulum;
Relaxation of the muscle fiber after contraction occurs as a result of active reverse transport of Ca 2+ from the cytoplasm to the sarcoplasmic reticulum.
7. The endings of the motor axon form neuromuscular connections with the muscle fibers of the motor unit of the corresponding motor neuron. Each muscle fiber is innervated by a branch of only one motor neuron:
ACh released from motor nerve endings upon receipt of the motor neuron action potential binds to the receptors of the motor end plate of the muscle membrane; ion channels open, allowing Na + and K + to pass through, due to which the end plate depolarizes;
A single motor neuron action potential is sufficient to elicit an action potential in a skeletal muscle fiber.
8. There is a certain sequence of processes leading to the contraction of the skeletal muscle fiber.
9. The concept of "reduction" refers to the inclusion of the operating cycle of the cross bridges. Whether the length of the muscle changes in this case depends on the action of external forces on it.
10. When a muscle fiber is activated, three types of contraction are possible:
Isometric contraction, when the muscle generates tension, but its length does not change;
Isotonic contraction, when the muscle shortens, moving the load;
A lengthening contraction is when an external load causes the muscle to lengthen during contractile activity.
11. An increase in the frequency of action potentials of the muscle fiber is accompanied by an increase in the mechanical reaction (tension or shortening) until the maximum level of tetanic tension is reached.
12. The maximum isometric tetanic tension develops in the case of the optimal length of the sarcomere L o. When the fiber is stretched more than its optimal length or the fiber length is reduced to less than L0, the voltage generated by it drops.
13. The speed of muscle fiber shortening decreases with increasing load. The maximum speed corresponds to zero load.
14. ATP is formed in muscle fibers in the following ways: transfer of phosphate from creatine phosphate to ADP; oxidative phosphorylation of ADP in mitochondria; substrate phosphorylation of ADP during glycolysis.
15.In the beginning exercise Muscle glycogen is the main source of energy. During longer exercise, energy is generated mainly by glucose and fatty acids coming from the blood; as you continue physical activity the role of fatty acids increases. When the intensity of physical work exceeds ~70% of the maximum, an increasingly significant part of the ATP formed begins to be provided by glycolysis.
16. Muscle fatigue is caused by a number of factors, including changes in the acidity of the intracellular environment, a decrease in glycogen stores, a violation of electromechanical coupling, but not ATP depletion.
17. There are three types of skeletal muscle fibers depending on the maximum shortening rate and the predominant method of ATP formation: slow oxidative, fast oxidative and fast glycolytic:
Miscellaneous maximum speed shortening of fast and slow fibers is due to differences in myosin ATPase: fast and slow fibers correspond to high and low ATPase activity;
Fast glycolytic fibers have, on average, a larger diameter than oxidative ones, and therefore develop more significant tension, but they get tired faster.
18.All muscle fibers of the same motor unit belong to the same type; most muscles contain all three types of motor units.
19. Characteristics of three types of skeletal muscle fibers are known.
20. The tension of the whole muscle depends on the amount of tension developed by each fiber, and on the number of active fibers in the muscle.
21. Muscles that perform subtle movements, consist of motor units with a small number of fibers, while big muscles, which ensure the maintenance of body posture, consist of much larger motor units.
22. Fast glycolytic motor units contain fibers of a larger diameter and, in addition, their motor units have a greater number of fibers.
23. An increase in muscle tension occurs primarily by increasing the number of active motor units, i.e. their involvement. At the beginning of the contraction, slow oxidative motor units are recruited first, then fast oxidative motor units, and finally, already at a very intense contraction, fast glycolytic units.
24. The involvement of motor units is accompanied by an increase in the speed with which the muscle moves the load.
25. The strength and fatigue of a muscle can be changed through training:
Long-term, low-intensity exercise increases the ability of muscle fibers to produce ATP through the oxidative (aerobic) pathway. This is due to an increase in the number of mitochondria and blood vessels in the muscle. As a result, muscle endurance increases;
Short-term high-intensity exercise increases fiber diameter due to increased actin and myosin synthesis. As a result, muscle strength increases.
26. Joint movements are carried out by means of two antagonistic muscle groups: flexors and extensors.
27. Muscles, together with bones, are systems of levers; in order for the limb to hold the load, the isometric tension of the muscle must significantly exceed the mass of this load, but the speed of movement of the lever arm is much greater than the speed of muscle shortening.
Smooth muscles
1. Smooth muscles can be classified into two large groups: unitary smooth muscles and multiunit smooth muscles.
2. Smooth muscle fibers - spindle-shaped cells without transverse striation, with one nucleus, capable of division. They contain actin and myosin filaments and contract through a mechanism sliding threads.
3. Increasing the concentration of Ca 2+ in the cytoplasm leads to the binding of Ca 2+ with calmodulin. The Ca 2+-calmodulin complex then binds to myosin light chain kinase, activating this myosin phosphorylating enzyme. Only after phosphorylation
smooth muscle myosin can bind to actin and carry out cyclic movements of cross bridges.
4. Myosin of smooth muscles hydrolyzes ATP at a relatively low rate, so smooth muscles shorten much more slowly than striated ones. However, the stress per unit area cross section for smooth muscle is the same as for striated muscle.
5.Ca 2+ ions, which initiate smooth muscle contraction, come from two sources: the sarcoplasmic reticulum and the extracellular environment. As a result of the opening of the calcium channels of the plasma membrane and the sarcoplasmic reticulum, which is mediated by various factors, Ca 2+ enters the cytoplasm.
6. Most of the stimulating factors increase the cytoplasmic concentration of Ca 2+ not enough to activate all the transverse bridges of the cell. That is why factors that increase the concentration of Ca 2+ in the cytoplasm can increase smooth muscle tension.
7. There are certain types of stimuli that cause smooth muscle contraction due to the opening of calcium channels in the plasma membrane and sarcoplasmic reticulum.
8. In the plasma membrane of most smooth muscle cells (but not all), when it is depolarized, action potentials can be generated. The ascending phase of the smooth muscle action potential is due to the entry of Ca 2+ into the cell through the opened calcium channels.
9. In some smooth muscles, action potentials are generated spontaneously, in the absence of external stimuli. This is due to the fact that pacemaker potentials periodically arise in the plasma membrane, depolarizing the membrane to a threshold level.
10. Smooth muscle cells lack specialized end plates. Some smooth muscle fibers are exposed to the action of neurotransmitters released from varicose thickenings of a single branch of the nerve, and each fiber may be influenced by neurotransmitters from more than one neuron. The action of neurotransmitters on smooth muscle contractions can be either excitatory or inhibitory.
heart muscle
1. Action potentials with a fast response are recorded from atrial and ventricular myocardial fibers and from specialized fibers of the ventricular conduction system (Purkinje fibers). The action potential is characterized by a large amplitude, a steep rise and a relatively long plateau.
2. Slow response action potentials are recorded in SA and AV node cells and in abnormal cardiomyocytes that have been partially depolarized. An action potential is characterized by a less negative resting potential, smaller amplitude, less steep rise, and a shorter plateau than a fast response action potential. The increase is generated by the activation of Ca 2+ channels.
3. Action potentials are characterized by an effective refractory period (the phase of absolute refractoriness).
4. Automation is typical for some cells of the SA- and AV-nodes and for the cells of the conduction system of the ventricles. A sign of automaticity is the slow depolarization of the membrane during phase 4 (slow diastolic depolarization).
5. Normally, the SA node initiates an impulse that causes the heart to contract. This impulse propagates from the SA node through the atrial tissue and eventually reaches the AV node. After a delay in the AV node, the cardiac impulse propagates through the ventricles.
6. An increase in the length of myocardial fibers, as occurs with increased ventricular filling (preload) during diastole, causes a stronger contraction of the ventricles. The relationship between fiber length and contraction force is known as the Frank-Starling ratio or as the Frank-Starling law of the heart.
7. Despite the fact that the myocardium consists of individual cells separated from each other by membranes, the cardiomyocytes that make up the ventricles contract almost in unison, like the atrial cardiomyocytes. The myocardium functions as a syncytium with an all-or-nothing response to arousal. Conduction of excitation from cell to cell is carried out through highly permeable contacts - gap junctions, which connect the cytosols of adjacent cells.
Rice. 4-2. General ideas about the structure of various muscles (see table)
8. When excited, voltage-controlled calcium channels open, and extracellular Ca 2+ enters the cell. The influx of Ca 2+ promotes the release of Ca 2+ from the sarcoplasmic reticulum. An increased concentration of intracellular Ca 2+ causes contraction of myofilaments. Relaxation is accompanied by the restoration of the concentration of intracellular Ca 2+ to the level at rest by actively pumping Ca 2+ back into the sarcoplasmic reticulum and exchanging Ca 2+ for extracellular Na+ through the sarcolemma.
9. The speed and strength of contractions depend on the intracellular concentration of free ions
calcium. Force and speed are inversely proportional to each other, so that when there is no load, the speed is maximum. During isovolumic contraction, when there is no external shortening, the total load is maximum and the velocity is zero.
10. When the ventricles contract, the stretching of the muscle fibers with blood during its filling serves as a preload. Afterload is the aortic pressure over which the left ventricle pushes blood out.
11. Contractility reflects the work of the heart at given values of preload and afterload.
* The number of plus signs (+) indicates the relative size of the sarcoplasmic reticulum in a given muscle type.
Physiology of skeletal muscles
concept skeletal, or striated muscle refers to a group of muscle fibers connected by connective tissue (Fig. 4-3 A). Muscles are usually attached to bones by bundles of collagen fibers. tendons, located at both ends of the muscle. In some muscles, single fibers have the same length as the entire muscle, but in most cases the fibers are shorter and often angled to the longitudinal axis of the muscle. There are very long tendons, they are attached to the bone, remote from the end of the muscle. For example, some of the muscles that move the fingers are located in the forearm; moving our fingers, we feel how the muscles of the hand move. These muscles are connected to the fingers through long tendons.
When studied with a light microscope, the main characteristic of skeletal muscle fibers was the alternation of light and dark stripes transverse to the long axis of the fiber. Therefore, skeletal muscles were named striated.
The transverse striation of skeletal muscle fibers is due to the special distribution in their cytoplasm of numerous thick and thin "threads" (filaments) that combine into cylindrical bundles with a diameter of 1-2 microns - myofibrils(Fig. 4-3 B). The muscle fiber is almost filled with myofibrils, they stretch along its entire length and are connected to tendons at both ends.
Thick and thin filaments form a periodic pattern along each myofibril. Thick filaments composed almost entirely of contractile protein myosin. Thin filaments(their thickness is about half the diameter of the thick filament) contain a contractile protein actin, as well as two other proteins - troponin
and tropomyosin playing important role in the regulation of contraction (see below).
Thick filaments are concentrated in the middle of each sarcomere where they lie parallel to each other; this region looks like a wide dark (anisotropic) band called A-stripe. Both halves of the sarcomere contain a set of thin filaments. One end of each of them is attached to the so-called Z-plate(or Z-line, or Z-band) - a network of intertwining protein molecules - and the other end overlaps with thick filaments. The sarcomere is limited by two consecutive Z-bands. Thus, the thin filaments of two adjacent sarcomeres are anchored on two sides of each Z-band.
Light (isotropic) band - the so-called I-band- located between the edges of the A-bands of two adjacent sarcomeres and consists of those sections of thin filaments that do not overlap with thick filaments. The Z-band bisects the I-band.
Within the A-band of each sarcomere, two more strips are distinguished. In the center of the A-band, a narrow light strip is visible - H-zone. It corresponds to the gap between the opposing ends of the two sets of thin filaments of each sarcomere, i.e. includes only the central parts of thick filaments. In the middle of the H-zone there is a very thin dark M-line. It is a network of proteins that connect the central parts of thick filaments. In addition, titin protein filaments go from the Z-band to the M-line, associated simultaneously with the M-line proteins and with thick filaments. The M-line and titin filaments maintain an orderly organization of thick filaments in the middle of each sarcomere. Thus, thick and thin filaments are not free, loose intracellular structures.
Rice. 4-3. The structure of skeletal muscles.
A - the organization of cylindrical fibers in skeletal muscle attached to the bones by tendons. B - structural organization of filaments in a skeletal muscle fiber, creating a pattern of transverse bands. Numerous myofibrils in a single muscle fiber are shown, as well as the organization of thick and thin filaments in a sarcomere.
actin molecule
It is a globular protein consisting of a single polypeptide that polymerizes with other actin molecules and forms two chains that wrap around each other (Fig. 4-4 A). Such a double helix is the backbone of a thin filament. Each actin molecule has a myosin binding site. In a resting muscle fiber, the interaction between actin and myosin is prevented by two proteins - troponin And tropomyosin(Fig. 4-4 B).
Tropomyosin is a rod-shaped molecule of two polypeptides wrapped around each other; the molecule corresponds in length to about seven actin monomers. End-to-end chains of tropomyosin molecules are located along the entire thin filament. Tropomyosin molecules partially cover the areas, interfering with the contact of myosin with actin. In this blocking position, the tropomyosin molecule is held by troponin.
Troponin is a heterotrimeric protein. It consists of troponin T (responsible for binding to a single molecule of tropomyosin), troponin C (binds the Ca 2+ ion), and troponin I (binds actin and inhibits contraction). Each tropomyosin molecule is associated with one heterotrimeric troponin molecule that regulates access to myosin binding sites on seven actin monomers adjacent to the tropomyosin molecule.
Myosin
This is a single name for a large family of proteins that have certain differences in the cells of different tissues. Myosin is present in all eukaryotes. About 60 years ago, two types of myosin were known, which are now called myosin I and myosin II. Myosin II was the first of the myosins discovered, and it is he who takes part in muscle contraction. Later, myosin I and myosin V were discovered (Fig. 4-4 C). Recently, it has been shown that myosin II is involved in muscle contraction, while myosin I and myosin V are involved in the work of the submembrane (cortical) cytoskeleton. More than 10 classes of myosin have been identified so far. Figure 4-4D shows two variants of the structure of myosin, which consists of a head, neck and tail. The myosin molecule consists of two large polypeptides (heavy chains) and four smaller ones (light chains). These polypeptides constitute a molecule with two globular "heads" that contain both kinds of chains, and a long rod ("tail") of two intertwined heavy chains. The tail of each myosin molecule is located along the axis of the thick filament, and two globular heads protrude from the sides, they are otherwise called cross bridges. Each globular head has two binding sites: for actin and for ATP. ATP binding sites also have the properties of the ATPase enzyme, which hydrolyzes the bound ATP molecule.
Figure 4-4 E shows the packing of myosin molecules. The protruding heads of myosin are the cross bridges.
Rice. 4-4. The structure of actin and myosin
At rest in the muscle fiber, the concentration of free, ionized Ca 2+ in the cytoplasm around thick and thin filaments is very low, about 10 -7 mol / l. At this concentration, Ca 2+ ions occupy a very small number of binding sites on troponin (troponin C) molecules, so tropomyosin blocks the binding of cross bridges to actin. After the action potential, the concentration of Ca 2+ ions in the cytoplasm increases rapidly, and they bind to troponin, eliminating the blocking effect of tropomyosin and initiating the cross-bridge cycle. The source of Ca 2+ entry into the cytoplasm is sarcoplasmic reticulum muscle fibre.
Sarcoplasmic reticulum muscle is homologous to the endoplasmic reticulum of other cells. It is located around each myofibril like a "torn sleeve", the segments of which are surrounded by A- and I-bands. The end parts of each segment expand in the form of so-called lateral sacs(terminal tanks) connected to each other by a series of thinner tubes. In the lateral sacs, Ca 2+ is deposited, which is released after the excitation of the plasma membrane (Fig. 4-5 A).
A separate system is transverse tubules (T-tubules), that cross the muscle fiber at the border lanes A-I, pass between the lateral sacs of two adjacent sarcomeres and exit to the surface of the fiber, forming a single whole with the plasma membrane. The lumen of the T-tubule is filled with extracellular fluid surrounding the muscle fiber (Fig. 4-5 B). The T-tubule membrane, like the plasma membrane, is capable of conducting an action potential. Having arisen in
plasma membrane (Fig. 4-5 C), the action potential quickly spreads along the surface of the fiber and along the membrane of T-tubules deep into the cell. Upon reaching the region of the T-tubules adjacent to the lateral sacs, the action potential activates voltage-dependent "gate" proteins of the T-tubule membrane, physically or chemically coupled to the calcium channels of the lateral sac membrane. Thus, the depolarization of the T-tubule membrane, caused by the action potential, leads to the opening of calcium channels in the membrane of the lateral sacs containing high concentrations of Ca 2+, and Ca 2+ ions are released into the cytoplasm. An increase in the cytoplasmic level of Ca 2+ is usually sufficient to activate all the cross-bridges of the muscle fiber.
The contraction process continues as long as Ca 2+ ions are bound to troponin, i.e. until their concentration in the cytoplasm returns to a low initial value. The membrane of the sarcoplasmic reticulum contains Ca-ATPase, an integral protein that actively transports Ca 2+ from the cytoplasm back to the cavity of the sarcoplasmic reticulum. As just mentioned, Ca 2+ is released from the reticulum as a result of the propagation of the action potential along the T-tubules; it takes much more time for Ca 2+ to return to the reticulum than for its exit. That is why the increased concentration of Ca 2+ in the cytoplasm persists for some time, and the contraction of the muscle fiber continues after the end of the action potential.
Summarize. The contraction is due to the release of Ca 2+ ions stored in the sarcoplasmic reticulum. When Ca 2+ enters back into the reticulum, contraction ends and relaxation begins.
Rice. 4-5. Sarcoplasmic reticulum and its role in the mechanism of muscle contraction.
A - diagram of the organization of the sarcoplasmic reticulum, transverse tubules and myofibrils. B - diagram of the anatomical structure of the transverse tubules and the sarcoplasmic reticulum in an individual skeletal muscle fiber. B - the role of the sarcoplasmic reticulum in the mechanism of skeletal muscle contraction
This is a sequence of processes by which the action potential of the plasma membrane of a muscle fiber leads to the initiation of muscle contraction or the so-called cross-bridge cycle, which will be demonstrated next.
The plasma membrane of skeletal muscle is electrically excitable and capable of generating a propagating action potential through a mechanism similar to that of nerve cells. The action potential in a skeletal muscle fiber lasts 1-2 ms and ends before any signs of mechanical activity appear (Fig. 4-6A). The mechanical activity that has begun can last for more than 100 ms. The electrical activity of the plasma membrane does not direct influence on contractile proteins, but causes an increase in the cytoplasmic concentration of Ca 2+ ions, which continue to activate the contractile apparatus even after the termination of the electrical process.
Muscle contraction
In muscle physiology, the term "contraction" is not necessarily to be understood as "shortening". First of all, the fact of activation of transverse bridges - areas of force generation in the muscle fiber is considered. After contraction, the mechanism that initiates the development of force is switched off.
The force with which a muscle, when it contracts, acts on an object is called muscular tension (tension); the force of an object (usually its mass) on a muscle is The forces of muscle tension and load counteract each other. Whether the force generated by a muscle fiber causes it to shorten depends on the relative magnitudes of the stress and
loads. In order for a muscle fiber to shorten and thus move the load, its tension must be greater than the opposing load.
isometric(the length of the muscle is constant). Such a contraction occurs when the muscle holds the load in a constant position or develops a force in relation to the load, the mass of which is greater than the muscle tension. If the muscle is shortened, and the load on it remains constant, the contraction is called isotonic
Sliding Thread Model
When the fiber is shortened, each cross bridge attached to the thin filament makes a turn like the rotation of a boat oar. Rotational movements of many transverse bridges pull thin filaments from both edges of the A-band to its middle, and the sarcomere shortens (Fig. 4-6 B). One "stroke" of the cross bridge creates very little movement of the thin filament relative to the thick one. However, over the entire period of the active state (excitation) of the muscle fiber, each transverse bridge repeats its rotational movement many times, providing a significant displacement of the myofilaments. The detailed molecular mechanism of this phenomenon will be considered below.
During the generation of a force that shortens the muscle fiber, the overlapping thick and thin filaments of each sarcomere, pulled up by the movements of the transverse bridges, shift relative to each other. The length of thick and thin filaments does not change with shortening of the sarcomere (Fig. 4-6 C). This mechanism of muscle contraction is known as sliding thread model.
Rice. 4-6. The phenomenon of electromechanical coupling.
A - the ratio between the time course of the action potential in the muscle fiber and the resulting contraction of the muscle fiber with its subsequent relaxation. B - cross bridges of thick filaments, binding to the actin of thin filaments, undergo a conformational change, due to which thin filaments are pulled to the middle of the sarcomere. (Only two of the approximately 200 cross-bridges of each thick filament are shown in the diagram.) B - model of sliding threads. Sliding of overlapping thick and thin filaments relative to each other leads to shortening of the myofibril without changing the length of the filaments. I-disk and H-zone are reduced
Specific skeletal muscle proteins
As noted, thick and thin filaments form a periodic pattern along each myofibril. A regularly repeated element is a sarcomere. Thick filaments are composed almost entirely of the contractile protein myosin. Thin filaments contain the contractile protein actin, troponin, and tropomyosin. Thick filaments are concentrated in the middle of each sarcomere, where they lie parallel to each other. This area has the appearance of a wide dark band called the A-band (Fig. 4-7 A). Both halves of the sarcomere contain a set of thin filaments. One end of each of them is attached to the so-called Z-band (or Z-line) - a network of intertwining protein molecules. The other end is overlapped with thick filaments. The sarcomere is limited by two consecutive Z-bands. Thus, the thin filaments of two adjacent sarcomeres are anchored on two sides of each Z-band. The light band - I-band, is located between the edges of the A-bands of two adjacent sarcomeres and consists of those sections of thin filaments that do not overlap with thick filaments. The Z-band bisects the I-band.
The two ends of each thick filament of the myosin molecule are oriented in opposite directions so that the ends of their tails are directed towards the center of the filament (Fig. 4-7 B). Due to this, during the rowing movements of the transverse bridges, the thin
the filaments of the left and right half of the sarcomere are pushed to its middle, as a result, the sarcomere is shortened. That is, during the generation of a force that shortens the muscle fiber, the overlapping thick and thin filaments of each sarcomere move relative to each other, pulled up by the movements of the transverse bridges. The length of thick and thin filaments does not change with shortening of the sarcomere
(Fig. 4-7 B).
It is known that within the A-band of each sarcomere, two more bands are distinguished. In the center of the A-band, a narrow light strip is visible - the H-zone. It corresponds to the gap between the opposing ends of the two sets of thin filaments of each sarcomere, i.e. includes only the central parts of thick filaments. In the middle of the H-zone is a very thin dark M-line. It is a network of proteins that connect the central parts of thick filaments. On fig. 4-7B show currently known additional proteins. Protein filaments go from the Z-band to the M-line titina, associated simultaneously with M-line proteins and with thick filaments. M-line And titin filaments maintain the ordered organization of thick filaments in the middle of each sarcomere. Thus, thick and thin filaments are not free, loose intracellular structures. In addition, in fig. 4-7V shown capz protein, determining the stabilization of actin filaments. Also shown tropomodulin. The figure also shows a giant protein - nebulin.
Rice. 4-7. The structure of the skeletal muscle is normal (A), against the background of relaxation (B) and contraction (C). Additional proteins found in skeletal muscle (D)
Actin and myosin molecule
Thin filament(Fig. 4-8 A) consists of actin, tropomyosin and troponin. The basis of a thin filament is a double twisted chain of an α-helical polymer of the actin molecule. In other words, these are two chains twisted relative to each other. Such a double helix is the backbone of a thin filament. Each helical turn of a single filament, or F-actin, consists of 13 single monomers in the form of globules and is approximately 70 nm long. Each single actin molecule has a myosin binding site. F-actin is associated with two important regulatory actin-binding proteins, tropomyosin and troponin. These proteins in the resting muscle fiber prevent the interaction between actin and myosin. Briefly, tropomyosin molecules partially cover the binding sites of each single actin molecule, interfering with the contact of myosin with actin. In this state of blocking the binding sites of each single actin molecule, the tropomyosin molecule retains troponin. Let's take a closer look at tropomyosin and troponin.
Tropomyosin is a long molecule consisting of two polypeptides wrapped around each other. The tropomyosin molecule corresponds in length to about seven actin monomers. End-to-end chains of tropomyosin molecules are located along the entire thin filament. Tropomyosin molecules partially cover areas binding of each actin molecule, blocking contact between myosin and actin. In this blocking position, the tropomyosin molecule is held by troponin.
Troponin is a heterotrimeric protein. It consists of troponin T, which is responsible for binding to a single molecule of tropomyosin, troponin C, which binds the Ca 2+ ion, and troponin I, which binds actin and inhibits contraction. Each tropomyosin molecule
It is associated with a single heterotrimeric troponin molecule that regulates access to myosin binding sites on seven actin monomers adjacent to the tropomyosin molecule.
Myosin molecule(Fig. 4-8 B) - a single name for a large family of proteins that have certain differences in the cells of different tissues. Involved in muscle contraction myosin II, the first of all myosins to open. In general, the myosin II molecule consists of two large polypeptides (so-called heavy chains) and four smaller ones (so-called light chains). Myosin II two heavy chains form a molecule containing two globular "heads"(one for each polypeptide) and, accordingly, two untwisted "necks". In some literature, the neck of the heavy chain is translated as "the arm of the myosin molecule". Next, two large polypeptides, i.e. two heavy chains begin to twist relative to each other. Their initial swirl region is called "hinge region of heavy chains". This is followed by a long rod of two intertwined heavy chains, called "tail". The tail of each myosin molecule is located along the axis of the thick filament, and two globular heads, along with necks and a hinge region, protruding on the sides, are otherwise called "cross bridges". Myosin II has two light chains on each globular head. One is the so-called light regulatory chain, the other is the light main chain. The light backbone is involved in the stabilization of the myosin head. The light regulatory chain regulates the activity of the myosin ATPase enzyme, which hydrolyzes the bound ATP molecule. The action of the light regulatory chain of myosin is to change the regulation through phosphorylation by Ca 2+ -dependent or Ca 2+ -independent kinases.
The interaction of the thin filament and a single pair of heads from the thick filament myosin is shown in Fig. 4-8 V.
Rice. 4-8. Molecular organization of thin and thick filaments.
A is a thin filament. B - myosin molecule. B - interaction of thin and thick filament
Interaction between actin and myosin
Consider the question of what allows cross bridges, i.e. globular heads (together with the necks and the hinge region), bind to actin and begin to make a certain movement. In the shortest possible time, muscle contraction is based on a cycle in which myosin II heads bind to actin binding sites. These cross bridges create a curvature that corresponds to the movement of the molecule, after which the myosin heads are separated from actin. For these cycles, the energy of ATP hydrolysis is taken. Muscles have mechanisms for regulating cross-bridge cycles. An increase in in initiates the continuation of the formation of cross-bridge cycles. When excited, there is an increase in in from the resting level (10 -7 M and less) to more than 10 -5 M.
To begin with, an action potential in a skeletal muscle fiber lasts 1-2 ms and ends before any signs of mechanical activity appear. The mechanical activity that has begun can last for more than 100 ms. Electrical activity of the plasma membrane does not directly influence on contractile proteins, but causes an increase in the cytoplasmic concentration of Ca 2+ ions, which continue to activate the contractile apparatus even after the termination of the electrical process. That is, the contraction is due to the release of Ca 2+ ions stored in the sarcoplasmic reticulum. When Ca 2+
returns to the reticulum, contraction ends and relaxation begins. The energy source for the calcium pump is ATP: this is one of the three main functions of ATP in muscle contraction.
So the reduction is initiated as a result of the increase in in . The heterotrimeric troponin molecule contains a key Ca 2+ -sensitive regulator, troponin C. Each troponin C molecule in skeletal muscle has two high-affinity Ca 2+ -binding sites that are involved in the binding of troponin C to the thin filament. Ca 2+ binding at these high affinity sites is constant and does not change during muscle activity. Each skeletal muscle troponin C molecule also has two additional low-affinity Ca 2+ binding sites. The interaction of Ca 2+ with them induces conformational changes in the troponin complex, leading to two effects. The first effect is that the C-terminus of inhibitory troponin I moves away from the actin-myosin binding site (located on actin), thereby moving the tropomyosin molecule also away from the actin-myosin binding site (located on actin). Another effect is through troponin T, and consists in pushing tropomyosin from the binding site of actin to myosin into the so-called actin groove. This causes the myosin-binding site on actin to open, and the myosin head can interact with actin, creating a cycle of cross-bridges.
Rice. 4-9. Principles of interaction between actin and myosin in skeletal and cardiac muscles
Reduction mechanism
The sequence of events from the binding of the cross bridge to the thin filament until the moment when the system is ready to repeat the process is called the working sequence. cross-bridge cycle. Each cycle consists of four main phases. Phase 1 - the myosin head is tightly bound to the actin molecule to form the actomyosin complex. ATP is required to detach the myosin head in the cytosol, and its approach to myosin is indicated by the arrow in the diagram. Phase 2 - if the myosin head binds to ATP, then the affinity of the myosin head for actin decreases. Due to the decrease in affinity, the myosin head separates from the actin molecule. When the effect on the myosin head of ATP is eliminated, the cycle continues further. In the muscle, this occurs solely due to the breakdown of ATP to ADP + R i as a result of the work of the myosin ATPase enzyme. This step depends on the presence of Mg 2+ . Phase 3 - if on the head of myosin after splitting of ATP into ADP and P i both ADP and P i are connected. In this case, the myosin head straightens. The affinity for the formation of the actomyosin complex again increases, and the myosin head can reattach the actin molecule with a weak bond. Phase 4 - the initiation of a weak bond quickly transitions into a stronger bond with the ADP-loaded myosin head. The transition to this state is actually a stage of force generation. This process is explained by the rotation of the myosin head, due to which the rotation of myosin shifts the actin filament by a step.
ATP plays two different roles in the cross-bridge cycle:
1)hydrolysis ATP supplies energy for the movement of the cross bridge;
2)binding(but not hydrolysis) ATP with myosin is accompanied by the separation of myosin from actin and creates the possibility of repeating the cycle of cross-bridges.
The chemical and physical phenomena during the four stages of the cross-bridge cycle can be represented differently. The myosin-bound ATP molecule is cleaved to release chemical energy and form the high-energy cross-bridge conformation of myosin; products of ATP-ADP hydrolysis and inorganic phosphate (Pi) remain bound to this form of myosin (M*).
The energy of the active conformation of myosin can be compared to the potential energy of a stretched spring.
actin binding.
When the high-energy form of myosin binds to actin, the release of the strained conformation of the high-energy cross-bridge is triggered; as a result, the actin-associated cross bridge performs its rotational movement and simultaneously loses ADP and P i .
Cross bridge movement.
The process of successively receiving and releasing energy by myosin can be compared to the work of a mousetrap. In it, energy is stored when the spring is stretched (in the muscle - during ATP hydrolysis), and released when the spring is released (in the muscle - when myosin binds to actin).
During the movement of the cross bridge, myosin is very strongly attached to actin; only after breaking this connection can he again receive energy and repeat the cycle. The bond between actin and myosin is broken when a new ATP molecule is attached to myosin.
Dissociation of the cross bridge from actin.
The separation of actin and myosin provided by ATP is an example of allosteric regulation of protein activity. The binding of ATP to one site of myosin reduces the affinity of its molecule for actin associated with another site. Therefore, ATP acts as a modulator that regulates the binding of actin to myosin. Note that at this stage, ATP is not cleaved; serves not as an energy source, but only as a modulating molecule that provides allosteric modulation of the myosin head and thereby weakens the binding of myosin to actin.
Rice. 4-10. reduction mechanism. The working cycle of cross bridges - myosin heads (together with the neck and hinge region) is presented.
Panel (A) shows the process as a closed cycle of four phases. Panel (B) shows the process as successive steps in more detail
Single muscle contraction
If a muscle develops tension but does not shorten (nor lengthen), the contraction is called isometric(the length of the muscle is constant). Such a contraction occurs when the muscle holds the load in a constant position, or develops a force in relation to the load, the mass of which is greater than the muscle tension. If the muscle is shortened, and the load on it remains constant, the contraction is called isotonic(muscle tension is constant).
The mechanical response of a single muscle fiber to a single action potential is called single contraction(twitch). The main characteristics of a single isometric contraction shown in fig. 4-11 A. The onset of muscle tension is delayed by a few milliseconds with respect to the action potential. During this latent period go through all the stages of electromechanical pairing. The interval from the beginning of voltage development to the moment of its maximum is reduction time. It is different for different types of skeletal muscle fibers. The contraction time of fast fibers does not exceed 10 ms, while for slower fibers it is not less than 100 ms. The duration of the contraction is determined by how long the cytoplasmic concentration of Ca 2+ remains elevated, ensuring the continuation of the cyclic activity of the cross bridges. The contraction time is due to the activity of Ca-ATPase of the sarcoplasmic reticulum, which is higher in fast fibers than in slow ones.
The characteristics of the isotonic contraction also depend on the mass of the lifted load (Fig. 4-11 B), namely, with a heavier load:
1) the latent period is longer;
2) the speed of shortening (the amount of shortening of the muscle per unit time), the duration of contraction and the amount of shortening of the muscle are less.
Comparison of single contractions of the same muscle fiber in different modes of its activity shows (Fig. 4-11 C) that the latent period is longer for isotonic contraction than for isometric contraction, while the duration of the mechanical process is shorter in the case of isotonic contraction (i.e. . when shortening) than isometric (i.e. when generating force).
Let us consider in more detail the sequence of phenomena during an isotonic single contraction. When a muscle fiber is excited, the cross bridges begin to develop force, but shortening does not begin until the muscle tension exceeds the load on the fiber. Thus, shortening is preceded by a period isometric Contraction, during which the voltage increases. The heavier the load, the longer it will take for the stress to equalize with the load and shortening begins. If the load is increased, then, in the end, the muscle fiber will not be able to lift it, the speed and degree of shortening will be equal to zero, and the contraction will become completely isometric.
Note that the force with which the muscle acts on the object during its contraction is called muscular tension (tension). The force of an object (usually its mass) on a muscle is The curve of muscle contraction in the domestic literature has long been called a "mechanogram", i.e. recording the mechanical activity of a muscle. In world literature, the concepts are usually used resting tension (force) to describe the force with which a resting muscle acts on an object (in mN), and active tension (force) to describe the force with which a muscle acts on an object when it contracts.
The forces of muscle tension and load counteract each other. Whether the force generated by a muscle fiber causes it to shorten depends on the relative magnitudes of stress and load. In order for a muscle fiber to shorten and thus transfer the load, its tension must be greater than the opposing load.
Rice. 4-11. Single muscle contraction.
A - single isometric contraction of a skeletal muscle fiber after one action potential. B - single isotonic contractions at different loads. The magnitude, speed, and duration of the shortening decrease with increasing load, while the time interval from the stimulus to the onset of the shortening increases with increasing load. B - single isotonic contraction of a skeletal muscle fiber after one action potential
Kinds muscle contractions
Since the duration of one action potential in a skeletal muscle fiber is 1-2 ms, and a single contraction can last 100 ms, the moment of initiation of the second action potential can fall within the period of mechanical activity. Figure 4-12 A-B shows isometric contractions of a muscle fiber in response to three successive stimuli. The isometric contraction in response to the first stimulus S 1 lasted 150 ms (Fig. 4-12 A). The second stimulus S2, given 200 ms after S1, when the muscle fiber had already completely relaxed, caused a second contraction identical to the first one, and the third stimulus S3 with the same interval caused the third identical contraction. In Figure 4-12B, the S 1 -S 2 interval remained at 200 ms, and the third stimulus was given 60 ms after S 2 , when the mechanical response to S 2 began to decline but had not yet ended. Stimulus S 3 caused a contractile response, the maximum voltage of which exceeded the response to S 2 . In Figure 4-12B, the S 2 -S 3 interval was reduced to 10 ms, and the maximum mechanical response increased even more, with the response to S 3 being a fused continuation of the response to S 2 .
An increase in muscle tension with successive action potentials occurring before the end of the phase of mechanical activity is called summation. When single contractions merge during rhythmic stimulation, tetanus(tetanic contraction). At low stimulus frequencies, the mechanical response may be undulating, as the fiber partially relaxes between stimuli; This serrated tetanus. If the frequency of stimulation is increased, a smooth tetanus is obtained, without oscillations (Fig. 4-12 D).
As the frequency of action potentials increases, the magnitude of the voltage increases as a result of summation until the smooth tetanus reaches a maximum, after which the voltage will not increase with a further increase in the frequency of stimulation.
To explain the causes of summation, it is necessary to consider what processes occur in muscle fibers. But first you need to get information about the elastic properties of the muscle. The muscle contains passive elastic elements (sections of thick and thin filaments, as well as tendons) connected in series with contractile elements (force generating). Sequential
the elastic elements act as springs through which the active force generated by the cross bridges is transmitted to the load. The time course of the voltage at isometric contraction includes the period required for the stretching of successive elastic elements.
The tension of a muscle fiber at a particular point in time depends on the following factors:
1) the number of cross bridges attached to actin and located at the 2nd stage of the cross bridge cycle in each sarcomere;
2) the force created by each cross bridge;
3) the duration of the active state of the transverse bridges.
One action potential causes the release of enough Ca 2+ in the muscle fiber to saturate troponin, so that all myosin binding sites on thin filaments are initially available. However, the binding of the high-energy form of the cross bridges to these areas (1st stage of the cross bridge cycle) takes some time, and in addition, as noted above, it takes time to stretch successive elastic elements. As a result, despite the initial accessibility of all binding sites during a single contraction, the maximum tension does not develop immediately. Another circumstance: almost immediately after the release of Ca 2+ ions, their reverse transfer to the sarcoplasmic reticulum begins, so that the concentration of Ca 2+ in the cytoplasm gradually decreases relative to the previous high level and, consequently, there are fewer and fewer myosin binding sites on actin filaments that can interact. with cross bridges.
The situation is different during tetanic contraction. Each next action potential causes the release of Ca 2+ from the sarcoplasmic reticulum before the reverse transfer of all Ca 2+ ions in the cytoplasm after the previous action potential ends. Due to this, an increased cytoplasmic concentration of Ca 2+ is sustainably maintained and, therefore, the number of sites available for binding to myosin on actin filaments does not decrease. As a result, the number of sites available for binding remains at the maximum level, the cyclic activity of the transverse bridges ensures sufficient stretching of successive elastic elements and the transfer of maximum stress to the ends of the muscle fiber.
Rice. 4-12. Relationship between frequency and voltage.
A-B - the summation of contractions as a result of a decrease in the time intervals between stimuli S 2 and S 3 . D - isometric contractions caused by a series of stimuli with a frequency of 10/s (serrated tetanus) and 100/s (fused tetanus); for comparison, a single contraction is shown
Relationship between load and shortening speed
The rate of shortening of the muscle fiber decreases with increasing load (Fig. 4-13 A). The shortening rate is maximum at no load and is zero when the load corresponds to the force of the maximum isometric stress. If the load becomes greater than the maximum isometric stress, there will be elongation muscle fiber at a rate that increases with increasing load; under a very large load, the fiber will break.
The rate of shortening is determined by the frequency of repetition of the working cycles of each cross bridge and, ultimately, the frequency of splitting of ATP molecules, since one ATP molecule is split in each cycle of the cross bridge. If the load on the cross bridge is increased, the ATP molecules are less likely to be hydrolyzed (for a number of reasons) and, consequently, the rate of truncation decreases.
Relationship between muscle length and tension
Passive The elastic properties of a relaxed muscle are mainly due to the peculiarities of the organization of the titin protein, the molecule of which is attached to the Z-band at one end, and to the thick filament at the other, and acts like a spring. As the muscle stretches, the passive tension of the relaxed fiber increases, but not due to the active movements of the transverse bridges, but due to the stretching of the titin filaments. If the stretched fiber is released, its length will return to its equilibrium state, just as a strip of rubber shortens in a similar situation. Stretching leads not only to the passive tension of the muscle fiber, but also to a change in its active tension during contraction. Therefore, the force generated during contraction depends on the initial length of the muscle fiber. This is illustrated by an experiment, when a muscle fiber is stretched, and at each length the amount of active tension is recorded in response to stimuli (Fig. 4-13 B). The length at which the fiber generates the greatest active isometric voltage is called optimal length,
With a muscle fiber length equal to 60% of L o , the fiber does not generate tension in response
for an incentive. As the fiber is stretched from this initial level, the active isometric stress increases at each length up to a maximum at length L o . During further elongation of the fiber, its stress falls. At a length of 175% or more of L o , the fiber does not respond to irritation.
When skeletal muscles are relaxed, the length of most of their fibers approaches L o and is therefore optimal for force generation. The length of the relaxed fibers changes under load or as a result of stretching due to the contraction of other muscles, but the passive change in the length of the relaxed fibers is limited because the muscles are attached to the bones. Passive length change rarely exceeds 30% and is often much less. In this range of values of the initial length, the active tension of the muscle never becomes lower than half of the tension developed at L o (Fig. 4-13 B).
The relationship between the initial length of a fiber and its ability to develop active stress during contraction can be explained in terms of the sliding filament model. When a relaxed muscle fiber is stretched, the thin filaments are pulled out of the thick filament bundles, so that the area of overlap is reduced. If the fiber is stretched to 1.75 L o , the filaments no longer overlap. The cross bridges cannot bind to actin and no tension develops. With less stretch (gradual change in length from 1.75 L o to L o ), the area of filament overlap increases, and the stress developed during stimulation increases in direct proportion to the increase in the number of cross bridges in the area of overlap. The largest area of overlap occurs at length L o ; then it can be attached to thin filaments the largest number cross bridges, and the generated voltage is maximum.
If the fiber length is less than L o , the developed voltage is reduced due to a number of circumstances. First, bundles of thin filaments from opposite ends of the sarcomere begin to overlap, interfering with the attachment of transverse bridges and the development of force. Secondly, for reasons that are not yet clear, with a decrease in fiber length, the troponin affinity for Ca 2+ decreases and, consequently, the number of sites available for binding to cross bridges on thin filaments decreases.
Rice. 4-13. Two main ratios: load - speed of muscle shortening, length - muscle tension.
A - the rate of shortening and lengthening of the skeletal muscle fiber depending on the load. Note that the force acting on the transverse bridges during the lengthening contraction is greater than the maximum isometric tension. B - changes in active isometric tetanic tension depending on the length of the muscle fiber. The blue area corresponds to the physiological range of fiber lengths in the muscle attached to the bone
The functional role of ATP in the process of skeletal muscle contraction
1. As a result of ATP hydrolysis caused by myosin, the cross bridges receive energy for the development of pulling force.
2. The binding of ATP to myosin is accompanied by the detachment of transverse bridges attached to actin.
3. Hydrolysis of ATP under the action of Ca-ATPase of the sarcoplasmic reticulum supplies energy for the active transport of Ca 2+ into the lateral sacs of the sarcoplasmic reticulum, which leads to a decrease in cytoplasmic Ca 2+ to the initial level. Accordingly, the contraction is completed, and the muscle fiber relaxes.
In skeletal muscles, during their transition from a state of rest to contractile activity - 20 times (or even several hundred times) the rate of ATP splitting sharply increases simultaneously. The small supply of ATP in skeletal muscle is sufficient for only a few single contractions. To sustain a sustained contraction, ATP molecules must be formed during metabolism at the same rate as they are broken down during contraction.
There are three ways ATP is generated during muscle fiber contraction (Figure 4-14):
1) ADP phosphorylation by transferring a phosphate group from creatine phosphate;
2) oxidative phosphorylation of ADP in mitochondria;
3) ADP phosphorylation during glycolysis in the cytoplasm.
Due to the phosphorylation of ADP by creatine phosphate, a very rapid formation of ATP is ensured at the very beginning of the contraction:
During the rest period, the concentration of creatine phosphate in the muscle fiber rises to a level approximately five times higher than the content of ATP. At the beginning of the contraction, when the ATP concentration begins to decrease and the ADP concentration begins to increase due to the breakdown of ATP by the action of myosin ATPase, the reaction shifts towards the formation of ATP due to creatine phosphate. In this case, the transition of energy occurs at such a high speed that at the beginning of the contraction
the concentration of ATP in the muscle fiber changes little, while the concentration of creatine phosphate falls rapidly.
Although ATP is formed from creatine phosphate very quickly, through a single enzymatic reaction, the amount of ATP is limited by the initial concentration of creatine phosphate in the cell. In order for a muscle contraction to last longer than a few seconds, the other two sources of ATP formation mentioned above must be involved. After the onset of the contraction provided by the use of creatine phosphate, the slower, multi-enzymatic pathways of oxidative phosphorylation and glycolysis are activated, due to which the rate of ATP formation increases to a level corresponding to the rate of ATP splitting.
With moderate muscle activity ATP is formed mainly by oxidative phosphorylation, and during the first 5-10 minutes, glycogen serves as the main resource for this. In the next ~30 min, blood-delivered energy sources become dominant, and glucose and fatty acids participate approximately equally. In the later stages of contraction, fatty acid utilization predominates, and glucose is consumed less.
If the intensity of muscle work is such that the rate of ATP breakdown exceeds 70% of its maximum level, the contribution of glycolysis to the formation of ATP increases significantly. Glucose for this process comes from two sources: from the blood or from glycogen stores in muscle fibers. As muscle activity increases, the proportion of ATP provided by the anaerobic process, glycolysis, increases; correspondingly more lactic acid is formed.
At the end of muscle work, the reserves of energy-rich compounds (creatine phosphate and glycogen) in the muscle are reduced. Energy is needed to restore the reserves of both compounds, so the muscle, already at rest, continues to intensively consume oxygen for some time. Due to the increased oxygen consumption in the period after muscular work, the so-called oxygen debt; and intensive formation of ATP by oxidative phosphorylation is aimed at restoring energy resources in the form of creatine phosphate and glycogen.
Rice. 4-14. Energy metabolism of skeletal muscle.
Three resources for the formation of ATP during muscle contraction: 1 - creatine phosphate; 2 - oxidative phosphorylation; 3 - glycolysis
Types of skeletal muscle fibers
Skeletal muscle fibers are not the same in their mechanical and metabolic features. Fiber types differ based on the following characteristics:
1) depending on the maximum speed of shortening - the fibers are fast and slow;
2) depending on the main pathway for the formation of ATP - oxidative and glycolytic fibers.
Fast and slow muscle fibers contain myosin isoenzymes that break down ATP at different maximum rates, which corresponds to a different maximum rate of the cross-bridge work cycle and, consequently, a different maximum rate of fiber shortening. High ATPase activity of myosin is characteristic of fast fibers, lower ATPase activity - slow fibers. Although the duty cycle is about 4 times faster in fast fibers than in slow fibers, both types of cross bridges generate the same force.
Another approach to the classification of skeletal muscle fibers is based on differences in the enzymatic mechanisms of ATP synthesis. Some fibers have many mitochondria and therefore provide a high level of oxidative phosphorylation; This oxidative fibers. The amount of ATP formed in them depends on the supply of the muscle with blood, from which oxygen molecules enter, and energy-rich compounds. Fibers of this type are surrounded by numerous capillaries. In addition, they contain an oxygen-binding protein - myoglobin, which increases the rate of oxygen diffusion, and also performs the function of a short-term oxygen depot in muscle tissue. Due to the significant content of myoglobin, oxidative fibers are colored dark red; they are often called red muscle fibers.
IN glycolytic fibers, on the contrary, there are few mitochondria, but a high content of glycolysis enzymes and large reserves of glycogen. These fibers are surrounded by a relatively small number of capillaries, and there is little myoglobin in their tissue, which corresponds to a limited use of oxygen. Due to lack
myoglobin glycolytic fibers look light and are called white muscle fibers.
Based on the two characteristics considered (speed of shortening and type of metabolism), three types of skeletal muscle fibers can be distinguished.
1.Slow oxidative fibers(type I) - low activity of myosin ATPase and high oxidative capacity (Fig. 4-15 A).
2.Fast oxidative fibers(type IIa) - high activity of myosin ATPase and high oxidative capacity (Fig. 4-15 B).
3.fast glycolytic fibers(type IIb) - high activity of myosin ATPase and high glycolytic capacity
(Fig. 4-15 B).
Note that the fourth theoretically possible variant, slow glycolytic fibers, has not been found.
Fibers vary not only in their biochemical characteristics, but also in size: glycolytic fibers have a significantly larger diameter than oxidative ones. This affects the magnitude of the voltage they develop. As for the number of thick and thin filaments per unit area of the cross section, it is approximately the same for all types of skeletal muscle fibers. Thus, the larger the diameter of the fiber, the greater the number of parallel thick and thin filaments involved in the generation of force, and the greater the maximum tension of the muscle fiber. It follows that the glycolytic fiber, which has a larger diameter, develops, on average, more significant tension, compared with the tension of the oxidative fiber.
In addition, the three types of muscle fibers considered are characterized by different resistance to fatigue. Fast glycolytic fibers get tired after a short time, while slow oxidative fibers are very hardy, which allows them to maintain contractile activity for a long time at an almost constant level of tension. Fast oxidative fibers occupy an intermediate place in their ability to resist the development of fatigue.
The characteristics of the three types of skeletal muscle fibers are summarized in Table 1. 4-1.
Rice. 4-15. Types of skeletal muscle fibers. The rate of development of fatigue in the fibers of three types.
Each vertical line corresponds to a contractile response to a brief tetanic stimulus. Contractile responses between the 9th and 60th minutes are missing
Table 4-1.Characteristics of the three types of skeletal muscle fibers
Muscle tension
The force with which a muscle acts on an object during its contraction is called muscular force. tension (tension); the force of an object (usually its mass) on a muscle is If the muscle is given a background load, as is usually done during measurements, then this background load is called preload - preload or prestretch. Often it is written in Russian spelling - "prelod". The forces of muscle tension and load counteract each other. Whether the force generated by a muscle fiber causes it to shorten depends on the relative magnitudes of stress and load. In order for a muscle fiber to shorten and thus move the load, its tension must be greater than the opposing load.
If a muscle develops tension but does not shorten (nor lengthen), the contraction is called isometric(the length of the muscle is constant) (Fig. 4-16 A). Such a contraction occurs when the muscle holds the load in a constant position or develops a force in relation to the load, the mass of which is greater than the muscle tension. If the muscle is shortened, and the load on it remains constant, the contraction is called isotonic(muscle tension is constant) (Fig. 4-16 B).
The third type of reduction is lengthening contraction (eccentric contraction), when the load acting on the muscle is greater than the tension developed by the transverse bridges. In such a situation, the load stretches the muscle, despite the opposing force created by the movements of the transverse bridges. An eccentric contraction occurs if the object supported by the muscle is displaced downward (examples: a person sits down from a standing position or walks down
stairs). It should be emphasized that under such conditions, the lengthening of muscle fibers is not an active process carried out by contractile proteins, but the result of an external force acting on the muscle. In the absence of an external force that lengthens the muscle, the fiber, when stimulated, will only shorten, but do not lengthen. All three types of contraction (isometric, isotonic and eccentric) are natural events of daily activities.
With each type of contraction, the transverse bridges rhythmically repeat a cycle consisting of four stages. In the 2nd stage of isotonic contraction, actin-associated cross-bridges rotate, causing the sarcomeres to shorten. It happens differently during isometric contraction: due to the load acting on the muscle, actin-related cross bridges cannot move thin filaments, but transfer force to them - isometric tension. During the 2nd stage of eccentric contraction, the cross bridges experience a load that pulls them back towards the Z-laminus, while they remain attached to actin and develop force. Stages 1, 3 and 4 are the same for all three types of contractions. Thus, with each type of contraction, the contractile proteins undergo the same chemical changes. The final result (shortening, no change in length or lengthening) is determined by the amount of load on the muscle.
Figure 4-16B shows the relationship "length-tension" during isometric contraction, and in Fig. 4-16 D, only the "active" fragment of this dependence, i.e. the difference between a "passive" curve and a general curve. Below are shown (Fig. 4-16 D) characteristic curves reflecting the load-speed relationship.
Rice. 4-16. Isometric and isotonic contraction.
A - an experimental drug for studying muscle contractions in isometric conditions. B - an experimental drug for studying muscle contractions under isotonic conditions. B - passive curve demonstrating muscle tension (tension), which is measured at various muscle lengths before contraction. Cumulative curve showing muscle tension (tension), which is measured at various muscle lengths during contraction. G - active muscle tension (active tension) is the difference between total and passive muscle tension on the panel (C). E - three blue curves show that the speed of muscle shortening is faster if the muscle is stretched with a mass
Musculoskeletal system
The contracting muscle transmits force to the bones through the tendons. If the force is sufficient, then when the muscle is shortened, the bones move. During contraction, the muscle develops only a pulling force, so that the bones to which it is attached, as it shortens, are pulled towards each other. In this case, it may happen bending limbs at the joint (flexion) or extension(extension) - straightening of the limb (Fig. 4-17 A). These oppositely directed movements must involve at least two different muscles - the flexor and extensor. muscle groups that move the joint in opposite directions are called antagonists. As shown in fig. 4-17 A, with contraction of the biceps muscle of the shoulder (m. biceps) arm bends into elbow joint, while contraction of the antagonist muscle - the triceps muscle of the shoulder (m. triceps) causes the arm to stretch. Both muscles create only a pulling force in relation to the forearm during contraction.
Antagonist muscle groups are necessary not only for flexion and extension, but also for movement of the limbs to the sides or for rotation. Some muscles, when contracted, can create two types of movement, depending on the contractile activity of other muscles acting on the same limb. For example, when reducing calf muscle(m. gastrocnemius) the leg bends at the knee, for example, while walking (Fig. 4-17 B). However, if the gastrocnemius muscle contracts simultaneously with the quadriceps femoris muscle (m. quadriceps femoris) which straightens the leg at the lower leg, the knee joint cannot flex, so movement is only possible at the ankle joint. There is an extension of the foot, i.e. a person rises on the tips of his toes - "stands on tiptoe."
The muscles, bones, and joints of the body are leverage systems. The principle of operation of the lever can be illustrated by the example of flexion of the forearm (Fig. 4-17B): the biceps muscle exerts a pulling force directed upwards on the area of \u200b\u200bthe forearm at a distance of about 5 cm from the elbow joint. In the example under consideration, the hand holds a load of 10 kg, i.e. at a distance of about 35 cm from the elbow, a downward force of 10 kg is acting. According to the laws of physics, the forearm is in a state of mechanical equilibrium (i.e., the total force acting on the system is zero) when the product of the downward force (10 kg) and the distance from the place of its application to the elbow (35 cm) is equal to the product of the isometric muscle tension (X) at a distance from it to the elbow (5 cm). So, 10x35=5xX; hence X = 70 kg. Note that the operation of this system is mechanically unfavorable, since the force developed by the muscle is much greater than the mass of the load being held (10 kg).
However, the mechanically unfavorable operating conditions of most muscle lever mechanisms are compensated by increasing maneuverability. Figure 4-17 shows that a 1 cm shortening of the biceps muscle corresponds to a hand movement of 7 cm. than the rate of muscle shortening. The lever system plays the role of an amplifier, thanks to which small, relatively slow movements biceps muscles are converted into faster hand movements. So a ball thrown by a pitcher on a basketball team travels at 90-100 mph (about 150-160 km/h), although the player's muscles shorten many times slower.
Rice. 4-17. Muscles and bones act as a system of leverage.
A - antagonist muscles that perform flexion and extension of the forearm. B - contraction of the gastrocnemius muscle leads to flexion of the lower limb when the quadriceps muscle of the thigh is relaxed, or to extension, when the latter contracts, not allowing knee joint bend. B - mechanical balance of forces acting on the forearm when the hand holds a load of 10 kg. D - the lever system of the arm acts as an amplifier in relation to the speed of contraction of the biceps muscle of the shoulder, increasing the speed of movement of the hand. The system is also an amplifier for the range of motion of the hand (when the muscle is shortened by 1 cm, the hand moves by 7 cm)
neuromuscular junction
The signal for triggering contraction is the action potential of the plasma membrane of the skeletal muscle fiber. In skeletal muscle, action potentials can only be elicited in one way - by stimulating nerve fibers.
Skeletal muscle fibers are innervated by axons of nerve cells called motoneurons(or somatic efferent neurons). The bodies of these cells are located in the brain stem or spinal cord. The axons of motor neurons are covered with a myelin sheath, and their diameter is larger than that of other axons, so they conduct action potentials with high speed, providing signals from the CNS to the skeletal muscle fibers with only a minimal delay.
Upon entering the muscle, the axon of the motor neuron divides into many branches, each of which forms one connection with the muscle fiber. One motor neuron innervates many muscle fibers, but each muscle fiber is controlled by a branch from only one motor neuron. The motor neuron, together with the muscle fibers it innervates, makes up motor unit. Muscle fibers of one motor unit are located in the same muscle, but not in the form of a compact group, but are scattered throughout the muscle. When an action potential arises in a motor neuron, all the muscle fibers of its motor unit receive a stimulus to contract.
When the axon approaches the surface of the muscle fiber, the myelin sheath ends, and the axon forms the terminal part (nerve ending) in the form of several short processes located in the grooves on the surface of the muscle fiber. The area of the plasma membrane of the muscle fiber, which lies directly under the nerve ending, has special properties and is called motor end plate. The structure consisting of a nerve ending and a motor end plate is known as neuromuscular junction(neuromuscular synapse).
The axon terminals of the motor neuron (motor nerve endings) contain vesicles filled with ACh. The action potential coming from the motor neuron depolarizes the plasma membrane of the nerve ending, as a result of which voltage-controlled Ca 2+ channels open, and Ca 2+ from the extracellular medium enters the nerve ending. Ca 2+ ions bind to proteins,
providing the fusion of the vesicle membrane with the plasma membrane of the nerve ending, and ACh is released into the synaptic cleft separating the nerve ending and the motor end plate. ACh molecules diffuse from the nerve ending to the motor end plate, where they bind to nicotinic-type acetylcholine receptors, opening ion channels permeable to both Na+ and K+. Due to the difference in transmembrane electrochemical gradients of these ions, the flow of Na + entering the muscle fiber is greater than the outgoing flow of K +, due to which local depolarization of the motor end plate occurs - end plate potential(PKP). PKP is similar to EPSP in interneuronal synapses. However, the amplitude of a single EPP is substantially higher than that of an EPSP because at the neuromuscular junction the released neurotransmitter hits a larger surface where it binds to a much larger number of receptors, and where, consequently, many more ion channels open. For this reason, the amplitude of a single PKP is usually more than sufficient for a local electrical current to occur in the region of the plasma muscle membrane adjacent to the end plate, initiating an action potential. The action potential then propagates along the surface of the muscle fiber through the same mechanism as in the axon membrane. Most of the neuromuscular junctions are located in the middle part of the muscle fiber, from where the resulting action potential propagates to both ends of the fiber. In human skeletal muscle, inhibitory potentials never occur. All neuromuscular connections are excitatory.
Along with ACh receptors, the motor end plate contains the enzyme aceticholinesterase(ACC-esterase), which cleaves ACH. As the concentration of free ACh decreases due to its cleavage by ACh-esterase, the amount of ACh that can bind to receptors decreases. When there are no ACh-bound receptors left, the end plate ion channels become closed. The end plate depolarization is completed, the membrane potential returns to the resting level, and the end plate is again able to respond to the ACh released when the next action potential arrives at the nerve ending.
Rice. 4-18. Muscle fiber membrane excitation: neuromuscular junction
Electromechanical interface
Early studies of the isolated heart revealed that optimal concentrations of Na + , K + and Ca 2+ are required for cardiac muscle contraction. Without Na +, the heart is unexcitable, it will not beat, since the action potential depends on extracellular sodium ions. On the contrary, the potential of the resting membrane does not depend on the transmembrane gradient of Na + ions. Under normal conditions, the extracellular concentration of K+ is about 4 mM. A decrease in the concentration of extracellular K + does not have a large effect on the excitation and contraction of the heart muscle. However, increasing the concentration of extracellular K + to a sufficient high levels causes depolarization, loss of excitability of myocardial cells and cardiac arrest in diastole. Ca 2+ is also essential for heart contractions. Removal of Ca 2+ from the extracellular fluid leads to a decrease in the strength of heart contractions and subsequent cardiac arrest in diastole. On the contrary, an increase in the concentration of extracellular Ca 2+ increases cardiac contractions, and very high concentrations of Ca 2+ lead to cardiac arrest in systole. Free intracellular Ca 2+ serves as an ion responsible for myocardial contractility.
The two panels of the figure show the mechanisms of electromechanical coupling in the heart, described below. Excitation of the heart muscle begins when a wave of excitation rapidly propagates along the sarcolemma of myocardial cells from cell to cell through gap junctions. Excitation also spreads into the cells through transverse tubes that are invaginated into the cardiac fibers in the Z-bands. Electrical stimulation in the area of the Z-band or application of ionized Ca 2+ in the area of the Z-band of cardiac fibers released from the membrane (with removed sarcolemmas) causes local contraction of neighboring myofibrils. During the plateau of the action potential, the permeability of the sarcolemma for Ca 2+ increases. Ca 2+ enters the cell along its electrochemical gradient through the calcium channels of the sarcolemma and its invaginations, i.e. through the membranes of the T-system.
It is believed that the opening of calcium channels occurs as a result of phosphorylation of channel proteins by cyclic adenosine monophosphate-dependent protein kinase (cAMP-dependent protein kinase). The initial source of extracellular Ca 2+ is the interstitial fluid (10 -3 M Ca 2+). Some
the amount of Ca 2+ may also be associated with the sarcolemma and with glycocalyx, mucopolysaccharide covering the sarcolemma. The amount of calcium entering the cell from the extracellular space is not enough to cause contraction of myofibrils. Entered inside calcium ("launching or trigger" Ca 2+) triggers the release of Ca 2+ from the sarcoplasmic reticulum (where there is a supply of intracellular Ca 2+). The concentration of free Ca 2+ in the cytoplasm increases from the level of rest (resting level) at about 10 -7 M to levels of 10 -6 to 10 -5 M at the time of excitation. Ca 2+ then binds to the troponin C protein. The calcium troponin complex interacts with tropomyosin to unblock active sites between actin and myosin filaments. This deblocking allows the formation of cyclic cross-links between actin and myosin and therefore allows the myofibrils to contract.
Mechanisms that increase the concentration of Ca 2+ in the cytosol increase the developed force of heart contractions (active force), and mechanisms that reduce the concentration of Ca 2+ in the cytosol reduce it. For example, catecholamines increase the entry of Ca 2+ into the cell by phosphorylation of channels through cAMP-dependent protein kinase. In addition, catecholamines, like other agonists, increase the strength of heart contractions by increasing the sensitivity of the contractile mechanism to Ca 2+. An increase in the concentration of extracellular Ca 2+ or a decrease in the Na + gradient through the sarcolemma also leads to an increase in the concentration of Ca 2+ in the cytosol.
The sodium gradient can be lowered by increasing the intracellular Na + concentration or by decreasing the extracellular Na + concentration. Cardiac glycosides increase the intracellular concentration of Na + by "poisoning" Na + /K + -ATPase, which leads to the accumulation of Na + in cells. An increase in the concentration of Na + in the cytosol changes the direction of the Na + / Ca 2+ exchanger (Na + /Ca 2+ -exchanger) to the opposite, so that less Ca 2+ is removed from the cell. The reduced concentration of extracellular Na + causes less Na + to enter the cell, and thus less Na + is replaced by Ca 2+ .
Achieved mechanical stress (tension) decreases due to a decrease in the concentration of extracellular Ca 2+, an increase in the transmembrane Na + gradient, or the use of Ca 2+ channel blockers that prevent Ca 2+ from entering myocardial cells.
Rice. 4-19. Electromechanical interface in the heart
Physiology of Smooth Muscles
Smooth muscle fiber is a fusiform cell with a diameter of 2 to 10 microns. Unlike multinucleated skeletal muscle fibers, which can no longer divide after differentiation is completed, smooth muscle fibers have a single nucleus and are capable of dividing throughout the life of the organism. Division begins in response to a variety of paracrine signals, often to tissue damage.
A significant variety of factors that modify the contractile activity of smooth muscles in various organs makes it difficult to classify smooth muscle fibers. However, there is a general principle based on the electrical characteristics of the plasma membrane. According to this principle, most smooth muscle can be classified into one of two types: unitary smooth muscles(single-unit smooth muscles) with fibers connected into a single whole (Fig. 4-20 A), the cells of which interact through gap junction, And multiunit smooth muscle(multiunit smooth muscles) with individual fiber innervation (Fig. 4-20 B).
Unitary smooth muscles
In muscles of this type, activity (electrical and mechanical) is carried out by different cells synchronously, i.e. the muscle responds to stimuli as a whole. This is due to the fact that muscle fibers are connected to each other. gap junction(gap junctions), through which the action potential can propagate from one cell to neighboring cells by means of local currents. Thus, the electrical activity that has arisen in any cell of unitary smooth muscles is transmitted to all fibers (Fig. 4-20 A).
Some fibers of unitary smooth muscles have pacemaker properties. They spontaneously generate action potentials that are conducted through gap junction to fibers that do not have such activity. Most unitary smooth muscle cells are not pacemaker.
The contractile activity of unitary smooth muscles is influenced by the electrical activity of the nerves, hormones, and local factors;
these influences are mediated by the mechanisms discussed above in relation to the activity of all smooth muscles. The nature of the innervation of unitary smooth muscles varies significantly in different organs. In many cases, the nerve endings are concentrated in those areas of the muscle where the pacemaker cells are located. The activity of the entire muscle can be regulated by changes in the frequency of the action potentials of the pacemaker cells.
Another feature of unitary smooth muscle is that its fibers often contract in response to stretch. Contractions occur when the walls of many hollow organs (for example, the uterus) are stretched, when the volume of their internal contents increases.
Examples of unitary smooth muscles: wall muscles gastrointestinal tract, uterus, thin blood vessels.
Multiunit smooth muscles
There are few multiunit smooth muscle cells between cells. gap junction, each fiber acts independently of its neighbors, and the muscle behaves like a set of independent elements. Multiunit smooth muscles are abundantly supplied with branches of autonomic nerves (Fig. 4-20 B). The overall response of the entire muscle depends on the number of activated fibers and on the frequency of nerve impulses. Although incoming nerve impulses are accompanied by depolarization and contractile responses of the fibers, action potentials are usually not generated in multiunit smooth muscles. The contractile activity of multiunit smooth muscles increases or decreases as a result of circulating hormones, but multiunit smooth muscles do not contract when stretched. Examples of multiunit smooth muscles: muscles in the walls of the bronchi and large arteries, etc.
It should be emphasized that most smooth muscles do not have the properties of exclusively unitary or multiunit smooth muscles. In fact, there is a continuum of smooth muscle variations with different combinations of properties of both types; unitary smooth muscle and multiunit smooth muscle are the two extremes.
Rice. 4-20. Structure of smooth muscles
Smooth muscle potentials
Some types of smooth muscle fibers generate action potentials spontaneously, in the absence of any neurogenic or hormonal influence. The resting potential of the plasma membrane of such fibers is not maintained at a constant level, but undergoes gradual depolarization until it reaches a threshold level and an action potential is generated. After repolarization of the membrane, its depolarization begins again (Fig. 4-21), so that a series of action potentials occurs, causing tonic contractile activity. Spontaneous potential shifts that depolarize the membrane to a threshold level are called pacemaker potentials.(As shown in other chapters, some cardiac muscle fibers and certain types of CNS neurons also have pacemaker potentials and can spontaneously generate action potentials in the absence of external stimuli.)
Interestingly, in smooth muscles capable of generating action potentials, Ca 2+ rather than Na+ ions serve as carriers of positive charges into the cell during the action potential rise phase; when the membrane is depolarized, voltage-gated calcium channels open, and action potentials in smooth muscles are of a calcium nature, and not sodium.
Unlike the striated muscle, in the smooth muscle the cytoplasmic concentration
cation Ca 2+ can increase (or decrease) as a result gradual depolarization (or hyperpolarization) shifts in the membrane potential, which increase (or decrease) the number of open calcium channels in the plasma membrane.
What role does extracellular Ca 2+ play in electromechanical coupling? There are two types of calcium channels in the plasma membrane of smooth muscle cells - voltage-dependent and controlled by chemical mediators. Since the concentration of Ca 2+ in the extracellular fluid is 10,000 times higher than in the cytoplasm, the opening of the calcium channels of the plasma membrane is accompanied by the entry of Ca 2+ into the cell. Due to the small size of the fiber, the Ca 2+ ions that have entered quickly reach intracellular binding sites by diffusion.
Another difference is that while in skeletal muscle a single action potential releases enough Ca 2+ to turn on all of the fiber's cross-bridges, in smooth muscle only a fraction of the cross-bridges are activated in response to most stimuli. That is why smooth muscle fibers generate tension gradually, as the cytoplasmic concentration of Ca 2+ changes. The greater the increase in Ca 2+ concentration, the greater the number of cross-bridges activated, and the greater the generated voltage.
Rice. 4-21. Electric potentials of smooth muscles
Sources of calcium entry into the cytoplasm
The increase in Ca 2+ concentration in the cytoplasm, due to which smooth muscle contraction is initiated, is provided from two sources: (1) the sarcoplasmic reticulum and (2) the extracellular environment, from which Ca 2+ enters the cell through the calcium channels of the plasma membrane. The relative contribution of these two sources of Ca 2+ varies for different smooth muscles. Some of them are more dependent on the extracellular concentration of Ca 2+ , others - on Ca 2+ deposited in the sarcoplasmic reticulum.
Sarcoplasmic reticulum of smooth muscles
As for the sarcoplasmic reticulum, it is less developed in smooth muscle than in skeletal muscle and does not have a specific organization that would correlate with the location of thick and thin filaments (Fig. 4-22 A). In addition, smooth muscle lacks T-tubules connected to the plasma membrane. Since the diameter of the smooth muscle fiber is small, and the contraction develops slowly, there is no functional need for the rapid propagation of the excitatory signal deep into the fiber. At the same time, special structures are observed between the sections of the plasma membrane and the sarcoplasmic reticulum,
analogous to specialized contacts between the membranes of T-tubules and lateral sacs in striated fibers. These structures mediate the interface between the action potential of the plasma membrane and the release of Ca 2+ from the sarcoplasmic reticulum. Secondary messengers released by the plasma membrane or formed in the cytoplasm in response to the binding of extracellular chemical mediators to plasma membrane receptors are involved in initiating the release of Ca 2+ from the regions of the sarcoplasmic reticulum located in the center of the fiber (Fig. 4-22 C).
In some smooth muscles, the Ca 2+ concentration is sufficient to maintain cross-bridge activity at a certain low level even in the absence of external stimuli. Such a phenomenon is called smooth muscle tone. The intensity of the tone is changed by the factors affecting the cytoplasmic concentration of Ca 2+ .
Removal of Ca 2+ from the cytoplasm, necessary for the fiber to relax, occurs through active transport of Ca 2+ back into the sarcoplasmic reticulum, as well as through the plasma membrane into the extracellular environment. The rate of removal of Ca 2+ in smooth muscle is much less than in skeletal muscle. Hence the different duration of a single contraction - a few seconds for a smooth muscle and a fraction of a second for a skeletal one.
The mechanisms of calcium metabolism are presented in
rice. 4-22 G.
Rice. 4-22. Sarcoplasmic reticulum of smooth muscles.
A - structure of the sarcoplasmic reticulum. B - sources of calcium intake through ion channels. B - sources of calcium intake through pumps and exchangers
Smooth muscle contractions
There are two types of filaments in the cytoplasm of smooth muscle fibers: thick myosin-containing and thin actin-containing. Thin filaments are attached either to the plasma membrane or to cytoplasmic structures - the so-called dense bodies(functional analogues of the Z-bands of striated fibers). In a relaxed smooth muscle fiber, filaments of both types are oriented at an oblique angle to the long axis of the cell. During fiber shortening, portions of the plasma membrane located between actin attachment points swell. The thick and thin filaments are not organized into myofibrils as in striated muscle and do not form regularly repeated sarcomeres, so there is no striation. However, smooth muscle contraction occurs through the mechanism of sliding filaments.
The concentration of myosin in smooth muscle is only about one third of that in striated muscle, while actin may be twice as high. Despite these differences, the maximum stress per unit cross-sectional area developed by smooth and skeletal muscles is similar.
The relationship between isometric tension and length for smooth muscle fibers is quantitatively the same as for skeletal muscle fibers. At the optimal fiber length, the maximum stress develops, and when the length shifts in both directions from its optimal value, the stress decreases. However, smooth muscle, compared with skeletal muscle, is able to develop tension in more wide range length values. This is an important adaptive property, given that most of the smooth muscles are part of the walls of hollow organs, with a change in the volume of which the length of the muscle fibers also changes. Even with relatively large increase in volume, as, for example, when filling the bladder, smooth muscle fibers in its walls retain to a certain extent the ability to develop tension; in striated fibers, such stretching could lead to the separation of thick and thin filaments beyond the zone of their overlap.
As in striated muscle, contractile activity in smooth muscle fibers is regulated by changes in the cytoplasmic concentration of Ca 2+ ions. However, these two types of muscles differ significantly in the mechanism of Ca 2+ influence on the activity of transverse bridges and changes in Ca 2+ concentration in response to stimulation.
Rice. 4-23. In smooth muscle, thick and thin filaments are oriented at an angle to the fiber axes and are attached to the plasma membrane or to dense bodies in the cytoplasm. When muscle cells are activated, thick and thin filaments slide against each other so that the cells shorten and thicken.
Activation of cross bridges
In the thin filaments of smooth muscles, there is no Ca 2+-binding protein troponin C, which mediates the trigger role of Ca 2+ in relation to the activity of transverse bridges in the skeletal muscle and in the myocardium. Instead, the cross-bridge cycle in smooth muscle is controlled by a Ca 2+-regulated myosin phosphorylating enzyme. Only the phosphorylated form of myosin in smooth muscle can bind to actin and provide cycles of cross-bridge movement.
Consider the process of smooth muscle contraction in detail. An increase in the level of Ca 2+ in the cytoplasm initiates a slow chain of events leading, on the one hand, to the release of the active site of binding to myosin on actin and, on the other hand, to an increase in the activity of myosin ATPase, and without this increase in the activity of myosin ATPase in smooth muscle, contraction cannot start.
The first phase of the process of activation of the myosin head is the binding of 4 Ca 2+ ions with calmodulin(CaM), which in this sense is very similar to troponin C of the striated muscle. Further, the Ca 2+ -CaM complex activates an enzyme called myosin light chain kinase(MLCM) (myosin light chain kinase, MLCK). MLCK contains an ATP-binding domain and an active site that ensures the transfer of phosphate from ATP to the acceptor protein. According to this mechanism, MLCK, in turn, phosphorylates the light regulatory chain associated with the head of the myosin II molecule. Phosphorylation of the light chain changes the conformation of the myosin II head, which is sufficiently altered by an increase in its ATPase activity to allow it to interact with actin. That is, the system works as a molecular motor (Fig. 4-23 A).
Figure 4-23B shows two independent cascades leading to smooth muscle contraction. Cascade (1) includes a mechanism for release from the blocking of the active center of actin, with which myosin must bind. Cascade (2) includes the mechanism of activation of the myosin head. The result of these two cascades is the formation of the actomyosin complex.
Let us consider the first cascade of release from blocking of the actin active site. Two proteins, caldesmon and calpomin, block actin from binding to myosin. Both are Ca 2+ -CaM binding proteins and both bind actin. On the one hand, Ca 2+ binds to CaM, and the Ca 2+-CaM complex acts in two ways on calponin. The first effect is that the Ca 2+ -CaM complex binds to calponin. The second effect is that the Ca 2+ -CaM complex activates Ca 2+ -CaM-dependent protein kinase, which phosphorylates calponin. Both effects reduce calponin's inhibition of ATPase
myosin activity. Caldesmon also inhibits the ATPase activity of smooth muscle myosin. On the other hand, Ca 2+ binds to CaM, and the Ca 2+-CaM complex binds via P i to caldesmon, which shifts the latter away from the actin-myosin binding site. The binding center on actin opens.
Consider the second cascade, which is presented in panel A. The first phase of the myosin head activation process consists in the binding of four Ca 2+ ions to CaM. The formed Ca 2+ -CaM complex activates MLCK. MLCK phosphorylates the regulatory light chain associated with the head of the myosin II molecule. Phosphorylation of the light chain changes the conformation of the myosin II head, which is sufficiently altered by an increase in its ATPase activity to allow it to interact with actin.
As a result, the actomyosin complex is formed.
The smooth muscle isoform of myosin ATPase is characterized by a very low maximum activity, about 10-100 times lower than the activity of skeletal muscle myosin ATPase. Since the rate of cyclic movements of the transverse bridges and, accordingly, the rate of shortening depends on the rate of ATP hydrolysis, smooth muscle contracts much more slowly than skeletal muscle. In addition, smooth muscle does not fatigue during prolonged activity.
In order for smooth muscle to relax after contraction, myosin dephosphorylation is necessary, since dephosphorylated myosin cannot be bound to actin. This process is catalyzed by myosin light chain phosphatase, which is active during the entire time of rest and smooth muscle contraction. With an increase in the cytoplasmic Ca 2+ concentration, the rate of myosin phosphorylation by active kinase becomes higher than the rate of its dephosphorylation by phosphatase, and the amount of phosphorylated myosin in the cell increases, providing the development of tension. When the concentration of Ca 2+ in the cytoplasm decreases, the rate of dephosphorylation becomes higher than the rate of phosphorylation, the amount of phosphorylated myosin falls, and smooth muscle relaxes.
When saving advanced level cytoplasmic Ca 2+, the rate of ATP hydrolysis by cross-bridge myosin decreases, despite the persisting isometric tension. If the phosphorylated cross-bridge attached to actin is dephosphorylated, it will be in a state of persistent rigid tension, remaining immobile. When such dephosphorylated cross-bridges bind to ATP, they dissociate from actin much more slowly. Thus, the ability of a smooth muscle to maintain tension for a long time with a low consumption of ATP is ensured.
As in skeletal muscle, the trigger stimulus for most smooth muscle contraction is an increase in the amount of intracellular calcium ions. In different types of smooth muscle, this increase can be caused by nerve stimulation, hormonal stimulation, stretching of the fiber, or even a change in the chemical composition of the environment surrounding the fiber.
However, in smooth muscle lacks troponin(a regulatory protein that is activated by calcium). Smooth muscle contraction is activated by a completely different mechanism, described below.
The connection of calcium ions with calmodulin. Myosin kinase activation and phosphorylation of the myosin head.
Instead of troponin smooth muscle cells contain large amounts of another regulatory protein called calmodulin. Although this protein is similar to troponin, it differs in the way the contraction is triggered. Calmodulin does this by activating myosin cross-bridges. Activation and reduction are carried out in the following sequence.
1. Calcium ions bind to calmodulin.
2. The calmodulin-calcium complex binds to the phosphorylating enzyme myosin kinase and activates it.
3. One of the light chains of each myosin head, called the regulatory chain, is phosphorylated by the action of myosin kinase. When this strand is not phosphorylated, there is no cyclic attachment and detachment of the myosin head relative to the actin filament. But when the regulatory chain is phosphorylated, the head acquires the ability to re-bind to the actin filament and carry out the entire cyclic process of periodic "pull-ups" that underlie contraction, as in skeletal muscle.
Termination of contraction. The role of myosinphosphatase. When the concentration of calcium ions falls below a critical level, the above processes automatically develop in the opposite direction, except for the phosphorylation of the myosin head. For the reverse development of this state, another enzyme, myosinphosphatase, is needed, which is localized in the fluids of the smooth muscle cell and cleaves the phosphatase from the regulatory light chain. After that, the cyclic activity, and hence the contraction, stops.
Therefore, the time necessary for muscle relaxation, is largely determined by the amount of active myosinphosphatase in the cell.
Possible mechanism for regulating the "latch" mechanism. Due to the importance of the “latch” mechanism in smooth muscle function, attempts are being made to explain this phenomenon, since it makes it possible to maintain long-term smooth muscle tone in many organs without significant energy costs. Among the many proposed mechanisms, we present one of the simplest.
When strongly activated and myosin kinase, and myosinphosphatase, the frequency of cycles of myosin heads and the rate of contraction are high. Then, as enzyme activation decreases, the frequency of cycles decreases, but at the same time, deactivation of these enzymes allows myosin heads to remain attached to actin filaments for an increasingly long part of the cycle. Therefore, the number of heads attached to an actin filament at any given time remains large.
Since the number heads attached to actin determines the static strength of the contraction, the tension is held, or "snaps". However, little energy is used, since there is no splitting of ATP to ADP, except in those rare cases when some head is detached.
Structurally, smooth muscle differs from striated skeletal muscle and cardiac muscle. It consists of spindle-shaped cells with a length of 10 to 500 microns, a width of 5-10 microns, containing one nucleus. Smooth muscle cells lie in the form of parallel oriented bundles, the distance between them is filled with collagen and elastic fibers, fibroblasts, feeding highways. The membranes of adjacent cells form nexuses that provide electrical communication between cells and serve to transmit excitation from cell to cell. In addition, the plasma membrane of a smooth muscle cell has special invaginations - caveolae, due to which the membrane area increases by 70%. Outside, the plasma membrane is covered by a basement membrane. The complex of the basement and plasma membranes is called the sarcolemma. Smooth muscle lacks sarcomeres. The contractile apparatus is based on myosin and actin protofibrils. There are much more actin protofibrils in SMC than in striated muscle fiber. Actin/myosin ratio = 5:1.
Thick and thin myofilaments are scattered throughout the sarcoplasm of a smooth myocyte and do not have such a slender organization as in striated skeletal muscle. In this case, thin filaments are attached to dense bodies. Some of these bodies are located on the inner surface of the sarcolemma, but most of them are in the sarcoplasm. Dense bodies are composed of alpha-actinin, a protein found in the Z-membrane structure of striated muscle fibers. Some of the dense bodies located on the inner surface of the membrane are in contact with the dense bodies of the adjacent cell. Thus, the force created by one cell can be transferred to the next. Thick myofilaments of smooth muscle contain myosin, while thin myofilaments contain actin and tropomyosin. At the same time, troponin was not found in the composition of thin myofilaments.
Smooth muscles are found in the walls of blood vessels, skin, and internal organs.
Smooth muscle plays an important role in the regulation
airway lumen,
vascular tone,
motor activity of the gastrointestinal tract,
uterus, etc.
Classification of smooth muscles:
Multiunitary, they are part of the ciliary muscle, the muscles of the iris of the eye, the muscle that lifts the hair.
Unitary (visceral), located in all internal organs, ducts of the digestive glands, blood and lymphatic vessels, skin.
Multiunit smooth muscle.
consists of separate smooth muscle cells, each of which is located independently of each other;
has a high density of innervation;
like striated muscle fibers, they are covered on the outside with a substance resembling a basement membrane, which includes insulating cells from each other, collagen and glycoprotein fibers;
each muscle cell can contract separately and its activity is regulated by nerve impulses;
Unitary smooth muscle (visceral).
is a layer or bundle, and the sarcolemmas of individual myocytes have multiple points of contact. This allows excitation to spread from one cell to another.
membranes of adjacent cells form multiple tight contacts(gap junctions), through which ions are able to move freely from one cell to another
the action potential arising on the membrane of the smooth muscle cell and ion currents can propagate along the muscle fiber, allowing the simultaneous contraction of a large number of individual cells. This type of interaction is known as functional syncytium
An important feature of smooth muscle cells is their ability to self-excitation (automatic), that is, they are able to generate an action potential without exposure to an external stimulus.
There is no constant resting membrane potential in smooth muscles, it constantly drifts and averages -50 mV. Drift occurs spontaneously, without any influence, and when the resting membrane potential reaches a critical level, an action potential arises, which causes muscle contraction. The duration of the action potential reaches several seconds, so the contraction can also last several seconds. The resulting excitation then spreads through the nexus to neighboring areas, causing them to contract.
Spontaneous (independent) activity is associated with stretching of smooth muscle cells, and when they stretch, an action potential occurs. The frequency of occurrence of action potentials depends on the degree of stretching of the fiber. For example, peristaltic contractions of the intestine are enhanced by stretching its walls with chyme.
Unitary muscles mainly contract under the influence of nerve impulses, but spontaneous contractions are sometimes possible. A single nerve impulse is not capable of causing a response. For its occurrence, it is necessary to sum up several impulses.
For all smooth muscles, during the generation of excitation, activation of calcium channels is characteristic, therefore, in smooth muscles, all processes are slower than in skeletal ones.
The speed of conduction of excitation along the nerve fibers to smooth muscles is 3-5 cm per second.
One of the important stimuli initiating contraction of smooth muscles is their stretching. Sufficient stretching of the smooth muscle is usually accompanied by the appearance of action potentials. Thus, the appearance of action potentials during smooth muscle stretching is promoted by two factors:
slow wave oscillations of the membrane potential;
depolarization caused by stretching of smooth muscle.
This property of smooth muscle allows it to automatically contract when stretched. For example, during the overflow of the small intestine, a peristaltic wave occurs, which promotes the contents.
Contraction of smooth muscle.
Smooth muscles, like striated muscles, contain cross-bridged myosin that hydrolyzes ATP and interacts with actin to cause contraction. In contrast to striated muscle, smooth muscle thin filaments contain only actin and tropomyosin and no troponin; the regulation of contractile activity in smooth muscles occurs due to the binding of Ca ++ to calmodulin, which activates myosin kinase, which phosphorylates the myosin regulatory chain. This results in ATP hydrolysis and starts the cross-bridge cycle. In smooth muscle, the movement of actomyosin bridges is a slower process. The breakdown of ATP molecules and the release of energy necessary to ensure the movement of actomyosin bridges does not occur as quickly as in striated muscle tissue.
Efficiency of energy consumption in smooth muscle is extremely important in the overall energy consumption of the body, since the blood vessels, small intestine, bladder, gallbladder and other internal organs are constantly in good shape.
During contraction, smooth muscle is able to shorten up to 2/3 of its original length (skeletal muscle 1/4 to 1/3 of its length). This allows the hollow organs to perform their function by changing their lumen to a significant extent.
Important properties of smooth muscle is its great plasticity, i.e., the ability to maintain the length given by stretching without changing the stress. The difference between skeletal muscle, which has little plasticity, and smooth muscle, with well-defined plasticity, is easily detected if they are first slowly stretched, and then the tensile load is removed. immediately shortened after the load is removed. In contrast, the smooth muscle after the removal of the load remains stretched until, under the influence of some kind of irritation, its active contraction occurs.
The property of plasticity is very important for the normal activity of the smooth muscles of the walls of hollow organs, such as the bladder: due to the plasticity of the smooth muscles of the walls of the bladder, the pressure inside it changes relatively little with different degrees of filling.
Excitability and arousal
Smooth muscles less excitable than skeletal ones: their thresholds of irritation are higher, and the chronaxy is longer. The action potentials of most smooth muscle fibers have a small amplitude (about 60 mV instead of 120 mV in skeletal muscle fibers) and a long duration - up to 1-3 seconds. On rice. 151 shows the action potential of a single fiber of the uterine muscle.
The refractory period lasts for the entire period of the action potential, i.e. 1-3 seconds. The rate of excitation conduction varies in different fibers from a few millimeters to several centimeters per second.
There are a large number of different types of smooth muscle in the body of animals and humans. Most of the hollow organs of the body are lined with smooth muscles that have a sensitial type of structure. The individual fibers of such muscles are very closely adjacent to each other and it seems that morphologically they form a single whole.
However, electron microscopic studies have shown that there is no membrane and protoplasmic continuity between the individual fibers of the muscular syncytium: they are separated from each other by thin (200-500 Å) slits. The concept of "syncytial structure" is currently more physiological than morphological.
syncytium- this is a functional formation that ensures that action potentials and slow waves of depolarization can freely propagate from one fiber to another. Nerve endings are located only on a small number of syncytium fibers. However, due to the unhindered spread of excitation from one fiber to another, the involvement of the entire muscle in the reaction can occur if the nerve impulse arrives at a small number of muscle fibers.
Smooth muscle contraction
With a large force of a single irritation, smooth muscle contraction may occur. The latent period of a single contraction of this muscle is much longer than that of the skeletal muscle, reaching, for example, in the intestinal muscles of a rabbit 0.25-1 second. The duration of the contraction itself is also large ( rice. 152): in the stomach of a rabbit, it reaches 5 seconds, and in the stomach of a frog - 1 minute or more. Relaxation is especially slow after contraction. The wave of contraction propagates through the smooth muscles also very slowly, it travels only about 3 cm per second. But this slowness of the contractile activity of smooth muscles is combined with their great strength. Thus, the muscles of the stomach of birds are capable of lifting 1 kg per 1 cm2 of their cross section.
Smooth muscle tone
Due to the slowness of contraction, a smooth muscle, even with rare rhythmic stimuli (for a frog's stomach, 10-12 stimuli per minute is enough), easily passes into a long-term state of persistent contraction, reminiscent of tetanus of skeletal muscles. However, the energy expenditure during such a persistent contraction of the smooth muscle is very small, which distinguishes this contraction from the tetanus of the striated muscle.
The reasons why smooth muscles contract and relax much more slowly than skeletal muscles have not yet been fully elucidated. It is known that myofibrils of smooth muscle, like those of skeletal muscle, consist of myosin and actin. However, smooth muscles do not have striation, no Z membrane, and are much richer in sarcoplasm. Apparently, these features of the structure of smooth muscle waves determine the slow pace of the contractile process. This corresponds to a relatively low level of smooth muscle metabolism.
Smooth muscle automation
A characteristic feature of smooth muscles, which distinguishes them from skeletal muscles, is the ability for spontaneous automatic activity. Spontaneous contractions can be observed in the study of the smooth muscles of the stomach, intestines, gallbladder, ureters and a number of other smooth muscle organs.
Smooth muscle automation is of myogenic origin. It is inherent in the muscle fibers themselves and is regulated by nerve elements that are located in the walls of smooth muscle organs. The myogenic nature of automaticity has been proven by experiments on strips of muscles of the intestinal wall, freed by careful dissection from the adjacent nerve plexuses. Such strips, placed in a warm Ringer-Locke solution, which is saturated with oxygen, are capable of making automatic contractions. Subsequent histological examination revealed the absence of nerve cells in these muscle strips.
In smooth muscle fibers, the following spontaneous oscillations of the membrane potential are distinguished: 1) slow waves of depolarization with a cycle duration of the order of several minutes and an amplitude of about 20 mV; 2) small rapid potential fluctuations preceding the emergence of action potentials; 3) action potentials.
Smooth muscle responds to all external influences by changing the frequency of spontaneous rhythm, which results in contraction and relaxation of the muscle. The effect of irritation of the smooth muscles of the intestine depends on the ratio between the frequency of stimulation and the natural frequency of spontaneous rhythm: with a low tone - with rare spontaneous action potentials - the applied irritation enhances the tone; with a high tone, relaxation occurs in response to irritation, since an excessive increase in impulses leads to that each next impulse falls into the refractory phase from the previous one.
Smooth muscle cells (SMCs) as part of smooth muscles form the muscular wall of hollow and tubular organs, controlling their motility and the size of the lumen. The contractile activity of SMCs is regulated by motor vegetative innervation and many humoral factors. In MMC no transverse striation, because myofilaments - thin (actin) and thick (myosin) threads - do not form myofibrils characteristic of striated muscle tissue. The pointed ends of the SMC are wedged between neighboring cells and form muscle bundles, which in turn form layers of smooth muscle. There are also single SMCs (for example, in the subendothelial layer of blood vessels).
contractile apparatus. Stable actin filaments are oriented predominantly along the longitudinal axis of the SMC and are attached to dense bodies. The assembly of thick (myosin) filaments and the interaction of actin and myosin filaments activate Ca 2+ ions coming from calcium depots - the sarcoplasmic reticulum. Indispensable components of the contractile apparatus - calmodulin(Ca 2+ -binding protein), kinase And light chain phosphatase myosin smooth muscle type.
Features of nervous influences. A feature of the innervation of skeletal muscles is the presence of the so-called motor units. The motor unit (motor unit) includes one motor neuron along with a group of innervated muscle fibers (from 10 to 2000). Motor neurons make up the nuclei or part of the nuclei of the cranial nerves or are located in the anterior horns of the spinal cord.
3) functioning of motor units.
a) From the neuron of the motor unit to the innervated muscle fibers, the impulse arrives simultaneously.
b) Usually, different neurons that make up the nerve centers do not send impulses to the periphery simultaneously, and the resulting asynchrony in the work of motor units ensures the unified nature of muscle contraction.
The resting potential of skeletal muscles is 60 - 90mV and is determined by the concentration gradient, mainly of K + ions tending to leave the cell. K - Na - dependent ATP-ase, using the energy of ATP, provides a constant injection of K + into the cell and the removal of Na +.
Action Potential muscle fibers is 110 - 120 mV, the duration of its phases is 1 - 3 ms (in the muscles of the limbs and trunk). The value of trace potentials varies within 15 mV, the duration is about 4 ms. The shape of the action potential is peaked.
5) Bioelectric phenomena and functional state.
Functional state muscles, the criterion of which is excitability, changes:
a) during the development of the action potential;
b) when the polarization of the membrane changes.
2.2 Smooth muscles.
1) Smooth muscle functions:
a) regulate the size of the lumen of hollow organs, bronchi, vessels;
b) move the contents with the help of a wave of contraction and changes in the tone of the sphincters.
2) electrophysiological phenomena.
resting potential smooth muscle fibers that do not have automation is 60 - 70 mV, with automation - ranges from 30 to 70 mV. The lower value of the resting potential in comparison with the striated muscle is explained by the fact that the membrane of the smooth muscle fiber is more permeable to sodium ions.
action potential. When excited in smooth muscles, two types of action potential can be generated:
a) peaked;
b) plateau.
The duration of peak-like action potentials is 5–80 ms, and that of plateau-like potentials is 90–500 ms.
The ionic mechanism of the action potential of smooth muscles differs from that of striated muscles. Depolarization of the smooth muscle fiber membrane is associated with the activation of slow, electrically excitable sodium-permeable calcium channels. Calcium channels are slow, that is, they have a long latent period of activation and inactivation.
3) functional units.
The functional unit of smooth muscle tissue is a bundle of fibers with a diameter of at least 100 microns. The bundle cells are connected by tight junctions or intercellular bridges. These circumstances lead to the fact that the activity of a section of smooth muscle tissue consists of the activity of functional units.
4) Features of the spread of excitation.
Excitation spreads in two ways:
a) by local currents, as in the nerve fiber and fibers of the striated muscle;
b) through necruses to neighboring muscle fibers (as in the heart muscle), since there is a functional syncytium.
5) Types of contractile activity associated with the functioning of the channels.
tonic contractions. Manifested in the form of basal tone and its changes. This is most pronounced in the sphincters. Provided by the inclusion of chemosensitive channels for ions Ca ++ , Na + .
Rhythmic (phasic) contractions. Manifested in the form of periodic activity. Phase contraction is triggered by an action potential and switching on of fast voltage-gated Ca++ and Na+ channels, followed by switching on of slow voltage-gated channels.
Under conditions of natural activity, a combination of tonic and phase components is usually observed, this is due to the inclusion of the above three types of channels. Inhibition of muscle activity is due to a decrease in the level of ionized calcium in the cell.
6) Smooth muscle automation and its regulation.
Smooth muscles are characterized by automaticity or spontaneous activity, the cause of which is rhythmic fluctuations in the membrane potential. So in the gastrointestinal tract, several sites are distinguished that perform the functions of a pacemaker - pacemakers (in the stomach, in the duodenum, ileum). Periodic expansion and narrowing of the lumen of microvessels is associated with the pacemaker activity of the smooth muscles of the vascular wall.
The functioning of the pacemaker.
Spontaneous activity depends on fluctuations in the concentration of Ca ++ and cAMP in pacemaker myocytes. Stages of events:
a) an increase in free calcium in the myocyte leads to the generation of an action potential;
b) adenylate cyclase is activated and the concentration of cAMP in the cell increases and calcium binds to intracellular depots or is removed from the cell;
Thus, the concentration of cAMP is a calcium oscillator or a rhythm-setting factor; as a result, one or another level of tonic tension (contraction) and slow movements are observed. In most cases, but not always, this is associated with a change in the activity of the metasympathetic nervous system.
Regulatory influence on the pacemaker is to regulate the rate of change in the concentration of cAMP, and hence the work of the calcium mechanism.
1) This is carried out due to the action of BAS on the metasympathetic system or directly on the pacemaker of the cell.
2) The influence of biologically active substances and the activity of the metasympathetic system are supplemented by the functioning of two sections of the ANS, the maximum activity of smooth muscles or its decrease is observed at a frequency of incoming impulses up to 12 per second:
a) usually the parasympathetic nervous system has an excitatory effect on smooth muscles, but relaxes the smooth muscles of blood vessels;
b) the sympathetic nervous system usually inhibits the activity of smooth muscles, but excites vascular smooth muscles;
3) The mechanism of contraction and relaxation of muscles (due to the knowledge of the issue, it is analyzed using the example of skeletal muscles).
